Tracking a serial killer: Integrating phylogenetic relationships, epidemiology, and geography for two invasive meningococcal disease outbreaks.

BackgroundWhile overall rates of meningococcal disease have been declining in the United States for the past several decades, New York City (NYC) has experienced two serogroup C meningococcal disease outbreaks in 2005-2006 and in 2010-2013. The outbreaks were centered within drug use and sexual networks, were difficult to control, and required vaccine campaigns.MethodsWhole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates collected before and during the two outbreaks. We integrated and analyzed epidemiologic, geographic, and genomic data to better understand transmission networks among patients. Betweenness centrality was used as a metric to understand the most important geographic nodes in the transmission networks. Comparative genomics was used to identify genes associated with the outbreaks.ResultsNeisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of isolates that were more distant from the outbreak strains, as well as those that should have been included based on high genomic similarity. Genomes for the second outbreak were more similar than the first and no polymorphism was found to either be unique or specific to either outbreak lineage. Betweenness centrality as applied to transmission networks based on phylogenetic analysis demonstrated that the outbreaks were transmitted within focal communities in NYC with few transmission events to other locations.ConclusionsNeisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help elucidate how it spreads geographically to facilitate targeted interventions to interrupt transmission

Sex Difference in Meningococcal Disease Mortality, New York City, 2008-2016

The case fatality rate (CFR) from invasive meningococcal disease (IMD) in New York City (NYC) is greater than national figures, with higher rates among females than males across all age groups. We conducted a retrospective cohort study among 151 persons aged ≥15 years diagnosed with IMD in NYC during 2008-2016 identified through communicable disease surveillance. We examined demographic, clinical, and community-level associations with death to confirm the elevated risk of mortality among female IMD patients after adjusting for confounders and to determine factors associated with female IMD mortality. Relative risks of death were estimated using multivariable log-linear Poisson regression with a robust error variance. Females had a higher CFR (n = 23/62; 37%) following IMD than males (n = 17/89; 19%) (adjusted relative risk [aRR], 2.1; 95% confidence interval [CI], 1.2-3.8). Controlling for demographic and clinical factors, there was a significant interaction between sex and fatal outcomes related to meningitis: the relative risk of death for females with meningitis was 13.7 (95% CI, 3.2-58.1) compared with males. In the model restricted to females, altered mental status (aRR, 7.5; 95% CI, 2.9-19.6) was significantly associated with an increased risk of death. Female mortality from IMD was significantly increased compared with males, controlling for other predictors of mortality. Sex-based differences in recognition and treatment need to be evaluated in cases of meningococcal disease. Our study highlights the importance of analyzing routine surveillance data to identify and address disparities in disease incidence and outcomes