title: Clinical laboratory response to a mock outbreak of invasive bacterial infections: a preparedness study.
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.
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA rjolsen@houstonmethodist.org.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.affiliation: Public Health Ontario, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nahuel
authors.initials: N
authors.lastname: Fittipaldi
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kachroo
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA Escuela de Biotecnologia y Alimentos and Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Nuevo León, Mexico.
authors.forename: Misu A
authors.initials: MA
authors.lastname: Sanson
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: S Wesley
authors.initials: SW
authors.lastname: Long
authors.affiliation: Infectious Disease Epidemiology, Prevention and Control Section, Minnesota Department of Health, St. Paul, Minnesota, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Como-Sabetti
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Chandni
authors.initials: C
authors.lastname: Valson
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Concepcion
authors.initials: C
authors.lastname: Cantu
authors.affiliation: Infectious Disease Epidemiology, Prevention and Control Section, Minnesota Department of Health, St. Paul, Minnesota, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lynfield
authors.affiliation: Respiratory Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Van Beneden
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Beres
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000818:Animals; D002170:Canada; D002959:Civil Defense; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D006302:Health Services Research; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D059021:Laboratory Proficiency Testing; D051379:Mice; D025202:Molecular Diagnostic Techniques / Q000379:methods; D013290:Streptococcal Infections / Q000175:diagnosis* / Q000453:epidemiology*; D013297:Streptococcus pyogenes / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D014481:United States