Tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing.
- Stucki D Swiss Tropical and Public Health Institute University of Basel.
- Ballif M Institute of Social and Preventive Medicine.
- Bodmer T Institute for Infectious Diseases, University of Bern labormedizinisches zentrum Dr Risch, Liebefeld-Bern.
- Coscolla M Swiss Tropical and Public Health Institute University of Basel.
- Maurer AM Cantonal Health Authorities Bern.
- Droz S Institute for Infectious Diseases, University of Bern.
- Butz C Bernese Lung Association.
- Borrell S Swiss Tropical and Public Health Institute University of Basel.
- Längle C Institute for Infectious Diseases, University of Bern.
- Feldmann J Swiss Tropical and Public Health Institute University of Basel.
- Furrer H Department of Infectious Diseases, Bern University Hospital and University of Bern.
- Mordasini C Bernese Lung Association.
- Helbling P Federal Office of Public Health, Bern.
- Rieder HL Institute of Social and Preventive Medicine, University of Zurich, Switzerland Tuberculosis Department, International Union Against Tuberculosis and Lung Disease, Paris, France.
- Egger M Institute of Social and Preventive Medicine School of Public Health and Family Medicine, University of Cape Town, South Africa.
- Gagneux S Swiss Tropical and Public Health Institute University of Basel.
- Fenner L Swiss Tropical and Public Health Institute University of Basel Institute of Social and Preventive Medicine.
- 2014-11-02
Published in:
- The Journal of infectious diseases. - 2015
genomic epidemiology
outbreak
screening
tuberculosis
whole genome sequencing
Adult
Aged
Bacterial Typing Techniques
DNA, Bacterial
Disease Outbreaks
Female
Genome, Bacterial
Genotype
Humans
Male
Middle Aged
Molecular Epidemiology
Mycobacterium tuberculosis
Polymorphism, Single Nucleotide
Retrospective Studies
Sequence Analysis, DNA
Switzerland
Tuberculosis
English
BACKGROUND
Whole-genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single-nucleotide polymorphism (SNP) typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland.
METHODS
On the basis of genome sequences of 3 historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1642 patient isolates and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected.
RESULTS
We identified 68 patients associated with the outbreak strain. Most received a tuberculosis diagnosis in 1991-1995, but cases were observed until 2011. Two thirds were homeless and/or substance abusers. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into 3 subclusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs.
CONCLUSIONS
Strain-specific SNP genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real time and at high resolution.
Whole-genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single-nucleotide polymorphism (SNP) typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland.
METHODS
On the basis of genome sequences of 3 historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1642 patient isolates and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected.
RESULTS
We identified 68 patients associated with the outbreak strain. Most received a tuberculosis diagnosis in 1991-1995, but cases were observed until 2011. Two thirds were homeless and/or substance abusers. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into 3 subclusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs.
CONCLUSIONS
Strain-specific SNP genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real time and at high resolution.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1093/infdis/jiu601
- PMID 25362193
- Persistent URL
- https://sonar.ch/global/documents/286578
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