Publications by authors named "Stefan Niemann"

Background: The integration of genomic and geospatial data into infectious disease transmission analyses typically includes residential locations and excludes other activity spaces where transmission may occur ( work, school, or social venues). The objective of this analysis was to explore residential as well as other activity spaces of tuberculosis (TB) outbreaks to identify potential geospatial 'hotspots' of transmission.

Methods: We analyzed data that included geospatial coordinates for residence and other activity spaces collected during 2012-2016 for the Kopanyo Study, a population-based study of TB transmission in Botswana.

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  • Haemophilus influenzae is a bacterial pathogen that can cause serious infections, and the rise of certain resistant strains is complicating treatment options for patients.
  • A study was conducted to analyze the relationship between genetic mutations in a specific protein (PBP3) and the bacteria's resistance to ampicillin and cefotaxime using a large dataset of clinical isolates.
  • Results showed that particular groups of PBP3 mutations were linked to increased resistance, while some strains previously thought to be susceptible actually displayed low specificity for ampicillin resistance, suggesting the need for updated diagnostic criteria.
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  • Extrapulmonary tuberculosis (EPTB) is difficult to diagnose due to nonspecific symptoms and various risk factors like age, sex, and HIV status, but the role of Mycobacterium tuberculosis complex (Mtbc) strain lineage is still debated.
  • A study analyzed clinical data from 1,035 patients over 15 years, finding that those with lineage 1 strains had higher odds of EPTB, but lineage was not a significant predictor when other factors were considered.
  • Geographic origin, female sex, and age were identified as stronger predictors for developing EPTB than the specific strain type, indicating a need for more research on how host factors interact with the pathogen.
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  • EnteroBase is a web-based platform that offers curated databases of genome sequences from over 1.1 million bacterial isolates, including notable pathogens like Streptococcus and Mycobacterium tuberculosis.
  • The platform now features tools for detecting antimicrobial resistance and a new bubble plot tool for visualizing bacterial genomic structures.
  • Enhanced access and functionalities are provided through a user-friendly interface and a RESTful API, with ongoing development by an international consortium to improve and maintain the system.
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Several human-adapted Mycobacterium tuberculosis complex (Mtbc) lineages exhibit a restricted geographical distribution globally. These lineages are hypothesized to transmit more effectively among sympatric hosts, that is, those that share the same geographical area, though this is yet to be confirmed while controlling for exposure, social networks and disease risk after exposure. Using pathogen genomic and contact tracing data from 2,279 tuberculosis cases linked to 12,749 contacts from three low-incidence cities, we show that geographically restricted Mtbc lineages were less transmissible than lineages that have a widespread global distribution.

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Species belonging to the complex (MKC) are frequently isolated from humans and the environment and can cause serious diseases. The most common MKC infections are caused by the species (), leading to tuberculosis-like disease. However, a broad spectrum of virulence, antimicrobial resistance and pathogenicity of these non-tuberculous mycobacteria (NTM) are observed across the MKC.

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  • - A Ukrainian patient was found to have an extensively drug-resistant (XDR) strain of tuberculosis with a specific rifampicin resistance mutation (RpoB I491F), which is not identified by standard testing methods.
  • - This situation highlights the difficulties in detecting and treating XDR-tuberculosis due to limitations in current rapid diagnostics recommended by the WHO.
  • - There is a pressing need for improved diagnostic tools and customized treatment plans, particularly in eastern Europe where these challenging strains are more common.
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  • The Mycobacterium avium complex (MAC) includes 12 species but focuses on M. avium, M. intracellulare subsp. intracellulare, and M. intracellulare subsp. chimaera, which are significant for clinical relevance in Central Europe.
  • Whole genome sequencing was performed on 610 MAC isolates from different countries, allowing for phylogenetic analysis and identification of resistance and virulence genes.
  • Results showed clustering of isolates with minimal SNP differences, but no clear correlation between genetic data and clinical outcomes, with specific species being less common in cases of extra-pulmonary disease.
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  • Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates can effectively predict which anti-tuberculosis drugs will work or not work against them.
  • Current methods for analyzing this data can be complex and hard to find, as many bioinformatic tools and mutation catalogs are tailored for specific needs.
  • This text offers a clear, step-by-step guide on how to process short-read sequencing data and reviews the analysis pipelines available for researchers.
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  • Whole genome sequencing (WGS) is increasingly used for testing antibiotic susceptibility in Mycobacterium tuberculosis complex (MTBC) isolates.
  • The process begins with DNA-library preparation, which involves creating unique short DNA fragments that represent the sample’s genomic content.
  • Existing protocols may require customization by labs to ensure effective implementation of WGS, so this text offers a detailed workflow adapted from an Illumina protocol to help reduce costs.
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Objectives: We evaluated the ability of FluoroType MTBDR version 2 (FTv2; Hain Lifescience), a second-step real-time PCR assay, to simultaneously detect Mycobacterium tuberculosis complex (MTBC) DNA and mutations conferring resistance to rifampicin (RIF) and isoniazid (INH), in pulmonary and extrapulmonary samples from patients and compared them with corresponding cultures.

Methods: FTv2 MTBC was evaluated on 1815 and 432 samples from Denmark (DK) and Germany (DE), respectively. RIF and INH resistance mutations were assessed in the German samples and 110 samples from Sierra Leone and subsequently compared to phenotypic antimicrobial susceptibility testing and a composite reference DNA (CRD) based on the GenoType MTBDR line-probe assay and Sanger sequencing or whole-genome sequencing.

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Background: We sought to identify resistance patterns and key drivers of recent multidrug-resistant tuberculosis (MDR-TB) transmission in a TB-prevalent area in Peru.

Methods: Cross-sectional study including MDR complex (Mtbc) strains identified in Callao-Peru between April 2017 and February 2019. Mtbc DNA was extracted for whole genome sequencing which was used for phylogenetic inference, clustering, and resistance mutation analyses.

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  • A study of a slow-growing non-tuberculous mycobacterium revealed it can cause pulmonary and extrapulmonary infections, yet its detailed genomic and clinical characteristics remain unclear.
  • Whole genome sequencing was performed on 33 isolates from seven patients over 14 years, correlating genomic data with clinical outcomes, highlighting low relevance in most cases.
  • The findings showed high genomic stability over time and no clear evidence of human-to-human transmission, suggesting that while transmission is possible, it is unlikely based on the current data.
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Bedaquiline is currently a key drug for treating multidrug-resistant or rifampin-resistant tuberculosis. We report and discuss the unusual development of resistance to bedaquiline in a teenager in Namibia, despite an optimal background regimen and adherence. The report highlights the risk for bedaquiline resistance development and the need for rapid drug-resistance testing.

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Introduction: Namibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.

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Unlabelled: Previous work reported unprecedented differences in the intrinsic susceptibility of the complex (MTBC) to pretomanid (Pa) using the Mycobacteria Growth Indicator Tube (MGIT) system. We tested 125 phylogenetically diverse strains from all known MTBC lineages (1-9) without known Pa resistance mutations and four strains with known resistance mutations as controls. This confirmed that MTBC, unlike most bacteria-antimicrobial combinations, displayed substantial differences in the intrinsic susceptibility relative to the technical variation of Pa MIC testing.

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Unlabelled: Multidrug-resistant tuberculosis (MDR-TB) management has become a serious global health challenge. Understanding its epidemic determinants on the regional level is crucial for developing effective control measures. We used whole genome sequencing data of 238 of complex (MTBC) strains to determine drug resistance profiles, phylogeny, and transmission dynamics of MDR/rifampicin-resistant (RR) MTBC strains from Sierra Leone.

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Objectives: Heteroresistant infections are defined as infections in which a mixture of drug-resistant and drug-susceptible populations are present. In (), heteroresistance poses a challenge in diagnosis and has been linked with poor treatment outcomes. We compared the analytical sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared with the 'gold standard' phenotypic assay: the agar proportion method (APM).

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Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages.

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  • * A new two-stage diagnostic workflow has been developed, allowing for rapid testing and drug susceptibility analysis from a single sputum sample, completed in just three days.
  • * The first stage utilizes automated qPCR to detect TB and resistance to key antibiotics, followed by targeted next generation sequencing (tNGS) for complete resistance profiling when necessary.
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Background: In 2021, an estimated 4800 people developed rifampicin-resistant tuberculosis in Mozambique, 75% of which went undiagnosed. Detailed molecular data on rifampicin-resistant and multidrug-resistant (MDR) tuberculosis are not available. Here, we aimed at gaining precise data on the determinants of rifampicin-resistant and MDR tuberculosis in Mozambique.

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