Tracking a Serial Killer: Integrating Phylogenetic Relationships, Epidemiology, and Geography for Two Invasive Meningococcal Disease Outbreaks

Abstract

31 Methods Whole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates33 collected before and during the two outbreaks. We integrated and analyzed epidemiologic, 34 geographic, and genomic data to better understand transmission networks among patients.35 Betweenness centrality was used as a metric to understand the most important geographic nodes 36 in the transmission networks. Comparative genomics was used to identify genes associated with 37 the outbreaks. 39 Results 40Neisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each 41 outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of 42 isolates that were more distant from the rest of the outbreak, as well as those that should have 43 been included based on high genomic similarity. Genomes for the second outbreak were more 44 similar than the first and no mutation was found to either be unique or specific to either outbreak 45 lineage. Betweenness centrality as applied to transmission networks based on phylogenetic for use under a CC0 license.This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/387597 doi: bioRxiv preprint first posted online Aug. 8, 2018; 3 46 analysis demonstrated that the outbreaks were transmitted within focal communities in NYC 47 with few transmission events to other locations. 49 Conclusions50 Neisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help 51 elucidate how it spreads geographically to facilitate targeted interventions to interrupt 52 transmission.for use under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. 65 N. meningitidis is found in the nasopharynx in up to 35% of healthy adults [11] and it is this66 colonization state that is believed to be responsible for IMD transmission and outbreaks.67 Secondary IMD cases are rare and outbreaks occur in either organizational settings, such as 68 universities, or in members of discreet community groups, such as MSM. Pulsed-field gel 69 electrophoresis (PFGE) has been used in NYC to detect links among IMD cases not identified by 70 case investigations [12]. However, PFGE may misclassify due to a lack of discriminatory power 71 [13]. Additionally, PFGE does not provide details on mutations in the N. meningitidis genome 72 that can be used to track its spread in space and time. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This art...