scholarly journals Robust barcoding and identification of Mycobacterium tuberculosis lineages for epidemiological and clinical studies

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Gary Napier ◽  
Susana Campino ◽  
Yared Merid ◽  
Markos Abebe ◽  
Yimtubezinash Woldeamanuel ◽  
...  
Keyword(s):  
Public Health ◽  
Mycobacterium Tuberculosis ◽  
Phylogenetic Tree ◽  
Snp Markers ◽  
Genomic Diversity ◽  
Whole Genome Sequencing Data ◽  
Global Public Health ◽  
Sequencing Data ◽  
Public Health Burden ◽  
And Control

Abstract Background Tuberculosis, caused by bacteria in the Mycobacterium tuberculosis complex (MTBC), is a major global public health burden. Strain-specific genomic diversity in the known lineages of MTBC is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Fast and accurate tracking of MTBC strains is therefore crucial for infection control, and our previous work developed a 62-single nucleotide polymorphism (SNP) barcode to inform on the phylogenetic identity of 7 human lineages and 64 sub-lineages. Methods To update this barcode, we analysed whole genome sequencing data from 35,298 MTBC isolates (~ 1 million SNPs) covering 9 main lineages and 3 similar animal-related species (M. tuberculosis var. bovis, M. tuberculosis var. caprae and M. tuberculosis var. orygis). The data was partitioned into training (N = 17,903, 50.7%) and test (N = 17,395, 49.3%) sets and were analysed using an integrated phylogenetic tree and population differentiation (FST) statistical approach. Results By constructing a phylogenetic tree on the training MTBC isolates, we characterised 90 lineages or sub-lineages or species, of which 30 are new, and identified 421 robust barcoding mutations, of which a minimal set of 90 was selected that included 20 markers from the 62-SNP barcode. The barcoding SNPs (90 and 421) discriminated perfectly the 86 MTBC isolate (sub-)lineages in the test set and could accurately reconstruct the clades across the combined 35k samples. Conclusions The validated 90 SNPs can be used for the rapid diagnosis and tracking of MTBC strains to assist public health surveillance and control. To facilitate this, the SNP markers have now been incorporated into the TB-Profiler informatics platform (https://github.com/jodyphelan/TBProfiler).

scholarly journals SplitStrains, a tool to identify and separate mixed Mycobacterium tuberculosis infections from WGS data

2021 ◽  
Author(s):  
Einar Gabbasov ◽  
Miguel Moreno-Molina ◽  
Iñaki Comas ◽  
Maxwell Libbrecht ◽  
Leonid Chindelevitch
Keyword(s):  
Public Health ◽  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Bacterial Pathogens ◽  
Superior Performance ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Sequencing Data ◽  
Multiple Strains

AbstractThe occurrence of multiple strains of a bacterial pathogen such as M. tuberculosis or C. difficile within a single human host, referred to as a mixed infection, has important implications for both healthcare and public health. However, methods for detecting it, and especially determining the proportion and identities of the underlying strains, from WGS (whole-genome sequencing) data, have been limited.In this paper we introduce SplitStrains, a novel method for addressing these challenges. Grounded in a rigorous statistical model, SplitStrains not only demonstrates superior performance in proportion estimation to other existing methods on both simulated as well as real M. tuberculosis data, but also successfully determines the identity of the underlying strains.We conclude that SplitStrains is a powerful addition to the existing toolkit of analytical methods for data coming from bacterial pathogens, and holds the promise of enabling previously inaccessible conclusions to be drawn in the realm of public health microbiology.Author summaryWhen multiple strains of a pathogenic organism are present in a patient, it may be necessary to not only detect this, but also to identify the individual strains. However, this problem has not yet been solved for bacterial pathogens processed via whole-genome sequencing. In this paper, we propose the SplitStrains algorithm for detecting multiple strains in a sample, identifying their proportions, and inferring their sequences, in the case of Mycobacterium tuberculosis. We test it on both simulated and real data, with encouraging results. We believe that our work opens new horizons in public health microbiology by allowing a more precise detection, identification and quantification of multiple infecting strains within a sample.

scholarly journals Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: an eco-epidemiological community-based cohort study in Brazil

2021 ◽  
Author(s):  
Max T Eyre ◽  
Fábio N Souza ◽  
Ticiana S. A. Carvalho-Pereira ◽  
Nivison Nery ◽  
Daiana de Oliveira ◽  
...  
Keyword(s):  
Public Health ◽  
Public Health Intervention ◽  
Spatial Modelling ◽  
The United States ◽  
Infection Risk ◽  
Human Infection ◽  
Global Public Health ◽  
Entire Study ◽  
Urban Settings ◽  
Public Health Burden

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. <br /><br />Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1,401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of ‘rattiness’, our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. <br /><br />Results: The estimated infection rate was 51.4 (95\%CI 40.4, 64.2) infections per 1,000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95\%CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95\%CI 1.05, 1.53). <br /><br />Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention.<br /><br />Funding: This work was supported by the Oswaldo Cruz Foundation and Secretariat of Health Surveillance, Brazilian Ministry of Health, the National Institutes of Health of the United States (grant numbers F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504 and R25 TW009338); the Wellcome Trust (102330/Z/13/Z), and by the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016). M.T.E is supported by an MRC doctorate studentship. F.N.S. participated in this study under a FAPESB doctorate scholarship.

scholarly journals Genetic diversity and drug susceptibility patterns of the Mycobacterium tuberculosis complex in Yunnan, China

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Ruolan Bai ◽  
Shuijing Chi ◽  
Xiaofei Li ◽  
Xiting Dai ◽  
Zhenhua Ji ◽  
...  
Keyword(s):  
Public Health ◽  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Public Health Problem ◽  
Drug Susceptibility ◽  
Drug Resistant ◽  
Global Public Health ◽  
High Genetic Diversity ◽  
Dominant Feature ◽  
Mdr Tb

AbstractTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) which has been threatening global public health for many years. High genetic diversity is dominant feature of Mtb. Increasing cases of multidrug-resistant (MDR) tuberculosis (MDR-TB) is a serious public health problem to TB control in China. Spontaneous mutations in the Mtb genome can alter proteins which are the target of drugs, making the bacteria drug resistant. The purpose of the present study was to analyze the genotype of Mtb isolates from some areas in Yunnan, China and explore the association between genotypes and MDR-TB. Using spoligotyping, we identified Beijing genotypes, six non-Beijing genotypes and a number of orphan genotypes from 270 Mtb isolates from patients in Yunnan Province during 2014–2016. Of 270 Mtb isolates, 102 clinical Mtb strains were identified as drug-resistant (DR) by drug susceptibility testing (DST), among them, 52 MDR strains. Beijing genotypes occupied the highest MDR proportion (78.85%) followed by the orphan genotypes (15.38%). The characteristics of MDR strains showed high genetic diversity. The results will help to efficiently improve diagnosis and treatment and provide valuable information for Mtb molecular epidemiology.

scholarly journals MTBseq: a comprehensive pipeline for whole genome sequence analysis of Mycobacterium tuberculosis complex isolates

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5895 ◽  
Author(s):  
Thomas Andreas Kohl ◽  
Christian Utpatel ◽  
Viola Schleusener ◽  
Maria Rosaria De Filippo ◽  
Patrick Beckert ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genome Sequence ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Whole Genome Sequencing Data ◽  
Phylogenomic Analysis ◽  
Whole Genome ◽  
Sequencing Data ◽  
Desktop Computer

Analyzing whole-genome sequencing data of Mycobacterium tuberculosis complex (MTBC) isolates in a standardized workflow enables both comprehensive antibiotic resistance profiling and outbreak surveillance with highest resolution up to the identification of recent transmission chains. Here, we present MTBseq, a bioinformatics pipeline for next-generation genome sequence data analysis of MTBC isolates. Employing a reference mapping based workflow, MTBseq reports detected variant positions annotated with known association to antibiotic resistance and performs a lineage classification based on phylogenetic single nucleotide polymorphisms (SNPs). When comparing multiple datasets, MTBseq provides a joint list of variants and a FASTA alignment of SNP positions for use in phylogenomic analysis, and identifies groups of related isolates. The pipeline is customizable, expandable and can be used on a desktop computer or laptop without any internet connection, ensuring mobile usage and data security. MTBseq and accompanying documentation is available from https://github.com/ngs-fzb/MTBseq_source.

scholarly journals Emerging Antimicrobial-Resistant High-Risk Klebsiella pneumoniae Clones ST307 and ST147

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Gisele Peirano ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
Johann D. D. Pitout
Keyword(s):  
Public Health ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
The United States ◽  
Medical Community ◽  
Global Public Health ◽  
African Countries ◽  
Content Type ◽  
Public Health Burden ◽  
Worldwide Distribution

ABSTRACT There is an enormous global public health burden due to antimicrobial-resistant (AMR) Klebsiella pneumoniae high-risk clones. K. pneumoniae ST307 and ST147 are recent additions to the family of successful clones in the species. Both clones likely emerged in Europe during the early to mid-1990s and, in a relatively short time, became prominent global pathogens, spreading to all continents (with the exception of Antarctica). ST307 and ST147 consist of multiple clades/clusters and are associated with various carbapenemases (i.e., KPCs, NDMs, OXA-48-like, and VIMs). ST307 is endemic in Italy, Colombia, the United States (Texas), and South Africa, while ST147 is endemic in India, Italy, Greece, and certain North African countries. Both clones have been introduced into regions of nonendemicity, leading to worldwide nosocomial outbreaks. Genomic studies showed ST307 and ST147 contain identical gyrA and parC mutations and likely obtained plasmids with blaCTX-M-15 during the early to mid-2000s, which aided in their global distribution. ST307 and ST147 then acquired plasmids with various carbapenemases during the late 2000s, establishing themselves as important AMR pathogens in certain regions. Both clones are likely underreported due to restricted detection methodologies. ST307 and ST147 have the ability to become major threats to public health due to their worldwide distribution, ability to cause serious infections, and association with AMR, including panresistance. The medical community at large, especially those concerned with antimicrobial resistance, should be aware of the looming threat posed by emerging AMR high-risk clones such as K. pneumoniae ST307 and ST147.

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