Clinical laboratory response to a mock outbreak of invasive bacterial infections: a preparedness study. Academic Article uri icon

Overview

abstract

  • Large hospital-based clinical laboratories must be prepared to rapidly investigate potential infectious disease outbreaks. To challenge the ability of our molecular diagnostics laboratory to use whole-genome sequencing in a potential outbreak scenario and identify impediments to these efforts, we studied 84 invasive serotype emm59 group A streptococcus (GAS) strains collected in the United States. We performed a rapid-response exercise to the mock outbreak scenario using whole-genome sequencing, genome-wide transcript analysis, and mouse virulence studies. The protocol changes installed in response to the lessons learned were tested in a second iteration. The initial investigation was completed in 9 days. Whole-genome sequencing showed that the invasive infections were caused by multiple subclones of epidemic emm59 GAS strains likely spread to the United States from Canada. The phylogenetic tree showed a strong temporal-spatial structure with diversity in mobile genetic element content, features that are useful for identifying closely related strains and possible transmission events. The genome data informed the epidemiology, identifying multiple patients who likely acquired the organisms through direct person-to-person transmission. Transcriptome analysis unexpectedly revealed significantly altered expression of genes encoding a two-component regulator and the hyaluronic acid capsule virulence factor. Mouse infection studies confirmed a high-virulence capacity of these emm59 organisms. Whole-genome sequencing, coupled with transcriptome analysis and animal virulence studies, can be rapidly performed in a clinical environment to effectively contribute to patient care decisions and public health maneuvers.

publication date

  • September 24, 2014

Research

keywords

  • Civil Defense
  • Disease Outbreaks
  • Laboratory Proficiency Testing
  • Streptococcal Infections
  • Streptococcus pyogenes

Identity

PubMed Central ID

  • PMC4313289

Scopus Document Identifier

  • 84910145818

Digital Object Identifier (DOI)

  • 10.1073/pnas.1321364111

PubMed ID

  • 25253790

Additional Document Info

volume

  • 52

issue

  • 12