Publication

Back to overview

Tracking a tuberculosis outbreak over 21 years: strain-specific single-nucleotide polymorphism typing combined with targeted whole-genome sequencing.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Stucki David, Ballif Marie, Bodmer Thomas, Coscolla Mireia, Maurer Anne-Marie, Droz Sara, Butz Christa, Borrell Sonia, Längle Christel, Feldmann Julia, Furrer Hansjakob, Mordasini Carlo, Helbling Peter, Rieder Hans L, Egger Matthias, Gagneux Sébastien, Fenner Lukas,
Project Swiss HIV Cohort Study (SHCS)
Show all

Original article (peer-reviewed)

Journal The Journal of infectious diseases
Volume (Issue) 211(8)
Page(s) 1306 - 16
Title of proceedings The Journal of infectious diseases
DOI 10.1093/infdis/jiu601

Open Access

URL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447836/
Type of Open Access Repository (Green Open Access)

Abstract

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. 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. 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. 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.
-