Whole genome sequencing for investigations of meningococcal outbreaks in the United States: a retrospective analysis

• Published in: Scientific reports Vol. 8; no. 1; pp. 15803 - 13
• Main Authors: Whaley, Melissa J., Joseph, Sandeep J., Retchless, Adam C., Kretz, Cecilia B., Blain, Amy, Hu, Fang, Chang, How-Yi, Mbaeyi, Sarah A., MacNeil, Jessica R., Read, Timothy D., Wang, Xin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 45/23; 631/326/107; 631/326/325; Bayesian analysis; Epidemics; Gel electrophoresis; Genomes; Genotypes; Humanities and Social Sciences; Meningococcal Outbreaks; multidisciplinary; Multilocus sequence typing; Nucleotide sequence; Outbreak Isolates; Outbreaks; PFGE Patterns; Phylogeny; Public health; Pulsed-field gel electrophoresis; Pulsed-field Gel Electrophoresis (PFGE); Recombination; Science; Science (multidisciplinary); Sporadic Isolates; Strains (organisms); United States > US; Sporadic Isolates; Pulsed-field Gel Electrophoresis (PFGE); Outbreak Isolates; Meningococcal Outbreaks; PFGE Patterns
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-33622-5

Although rare in the U.S., outbreaks due to Neisseria meningitidis do occur. Rapid, early outbreak detection is important for timely public health response. In this study, we characterized U.S. meningococcal isolates (N = 201) from 15 epidemiologically defined outbreaks (2009–2015) along with temporally and geographically matched sporadic isolates using multilocus sequence typing, pulsed-field gel electrophoresis (PFGE), and six whole genome sequencing (WGS) based methods. Recombination-corrected maximum likelihood (ML) and Bayesian phylogenies were reconstructed to identify genetically related outbreak isolates. All WGS analysis methods showed high degree of agreement and distinguished isolates with similar or indistinguishable PFGE patterns, or the same strain genotype. Ten outbreaks were caused by a single strain; 5 were due to multiple strains. Five sporadic isolates were phylogenetically related to 2 outbreaks. Analysis of 9 outbreaks using timed phylogenies identified the possible origin and estimated the approximate time that the most recent common ancestor emerged for outbreaks analyzed. U.S. meningococcal outbreaks were caused by single- or multiple-strain introduction, with organizational outbreaks mainly caused by a clonal strain and community outbreaks by divergent strains. WGS can infer linkage of meningococcal cases when epidemiological links are uncertain. Accurate identification of outbreak-associated cases requires both WGS typing and epidemiological data.