Supplementary file 1_Investigation of invasive Neisseria meningitidis serogroup Y ST1466 case increases in New York State.docx

Bacterial meningitis and septicemia caused by Neisseria meningitidis is a serious infection that requires immediate medical attention and prompt treatment. In the United States, cases of N. meningitidis serogroup Y increased sharply in 2023, leading to a CDC health advisory issued in March 2024, alerting public health agencies and healthcare providers of this surge. N. meningitidis serogroup Y is of particular concern because these strains demonstrate higher levels of resistance to the antimicrobials ciprofloxacin and penicillin. At the Wadsworth Center Bacteriology Laboratory (WCBL), all N. meningitidis isolates received are identified, serogroup determined by real-time PCR, and antimicrobial susceptibility testing is performed. A subset of isolates undergo whole genome sequencing (WGS) to determine the multilocus sequence type (MLST), presence of antimicrobial resistance genes, and relatedness analysis for outbreak investigations. In this study, we sequenced all 36 N. meningitidis serogroup Y isolates received between 2018 and 2024, of which 20 (~55%) were determined to be sequence type (ST) 1466. We used multiple bioinformatic methods to characterize the relatedness of isolates received at WCBL and compared them with ST1466 isolates from the United States with publicly accessible genomes. We identified a cluster of 8 cases of ST1466 N. meningitidis from the same region of New York State (NYS) that included a known transmission event linked to sharing a cigarette. Cases in this cluster were comprised of predominantly unvaccinated, African American, non-Hispanic, males between 45 and 76 years old, and mostly presented with sepsis; a demographic and clinical presentation not typical of those affected by N. meningitidis in the United States. Comparisons with publicly available genomes from ST1466 N. meningitidis strains from across the country showed that relatedness methods that mask genomic regions showing recombination signatures can obscure the diversity among these strains. This study, which importantly includes a case of known recent transmission, highlights the need to revisit genomic relatedness estimation and thresholds for defining relatedness in N. meningitidis. Our results also illuminate the importance of surveillance and characterization of N. meningitidis for future prevention and treatment, and the increased resolution that WGS provides to surveillance efforts.