Background:
Neisseria meningitidis (Nm) can cause invasive meningococcal disease (IMD), with a case fatality rate ranging from 10-15. Due to its high fatality rate, outbreaks of meningococcal disease remain a significant public health concern in the U.S. Most IMD cases are linked to serogroups B, C, W, and Y, although some involve nongroupable strains. While the incidence of IMD in the U.S. is typically low and outbreaks are rare, an increase in cases attributed to Nm serogroup Y (NmY) since 2022 is concerning.
Aim/Methods:
Nm isolates submitted to CDC as part of Enhanced Meningococcal Disease Surveillance January 2022 to December 2024 were analyzed. Whole-genome sequencing (WGS) was performed on the Illumina platform, and the resulting data were processed with the Bacterial Meningitis Genome Analysis Platform to predict serogroup, clonal complex (CC), and sequence type (ST) and to screen for antimicrobial resistance markers. WGS data were also used to assess genetic similarities among these isolates using phylogenetic and single nucleotide polymorphism (SNP) analyses.
Results:
Isolates were available at CDC for 1006/1270 cases reported from January 2022 to December 2024 (202/309 for 2022, 347/437 for 2023, and 387/524 for 2024). The rise in U.S. Nm cases starting in 2022 included primarily NmY ST-1466/CC174, which accounted for 15.8% (32/202) of available isolates in 2022, 40.3% (140/347) in 2023 and 25.8% (100/387) for the year 2024. These cases were reported across multiple jurisdictions, spanning 36 states. Comparison of WGS results revealed that all ST-1466 isolates studied were closely related, with an average SNP distance of 41 nucleotides, forming several closely related clusters. Genomic analysis also predicted that all ST-1466/CC174 isolates studied would be susceptible to penicillins and fluoroquinolones.
Conclusion:
The recent rise in IMD cases in the U.S. since 2022 has been largely attributed to NmY, particularly ST-1466, which was also identified in an ongoing outbreak that started in Virginia in 2022. This increase underscores the need for continued genomic surveillance to identify changes in circulating meningococcal strains and inform public health response to outbreaks.
Key Words: Sequence Type, Clonal complex, IMD, Meningitis, Whole-genome sequencing