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Background: Historically, antimicrobial resistance has been rare in US invasive meningococcal disease cases., Methods: Meningococcal isolates (n = 695) were collected through population-based surveillance, 2012-2016, and national surveillance, 2015-2016. Antimicrobial susceptibility was assessed by broth microdilution. Resistance mechanisms were characterized using whole-genome sequencing., Results: All isolates were susceptible to 6 antibiotics (cefotaxime, ceftriaxone, meropenem, rifampin, minocycline, and azithromycin). Approximately 25% were penicillin or ampicillin intermediate; among these, 79% contained mosaic penA gene mutations. Less than 1% of isolates were penicillin, ampicillin, ciprofloxacin, or levofloxacin resistant., Conclusions: Penicillin- and ampicillin-intermediate isolates were common, but resistance to clinically relevant antibiotics remained rare., (Published by Oxford University Press for the Infectious Diseases Society of America 2022.)

Background: We conducted a Neisseria meningitidis (Nm) carriage study among men who have sex with men (MSM) to explore possible sexual transmission., Methods: We paired information on patient characteristics with oropharyngeal, rectal, and urethral Nm culture results to assess associations with Nm carriage among 706 MSM at New York City sexual health clinics. The Nm isolates were characterized by whole genome sequencing., Results: Twenty-three percent (163 of 706) of MSM were Nm carriers. Oropharyngeal carriage was 22.6% (159 of 703), rectal 0.9% (6 of 695), and urethral 0.4% (3 of 696). Oropharyngeal carriage was associated with the following recent (past 30 days) exposures: 3 or more men kissed (adjusted relative risk [aRR], 1.38; 95% confidence interval [CI], 1.03-1.86), performing oral sex (aRR, 1.81; 95% CI, 1.04-3.18), and antibiotic use (aRR, 0.33; 95% CI, 0.19-0.57). Sixteen clonal complexes were identified; 27% belonged to invasive lineages., Conclusions: Our findings suggest that oral sex and the number of recent kissing partners contribute to Nm carriage in MSM.

In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population. IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis , can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.

Invasive meningococcal disease is mainly caused by Neisseria meningitidis serogroups A, B, C, X, W, and Y. The serogroup is typically determined by slide agglutination serogrouping (SASG) and real-time PCR (RT-PCR). We describe a whole-genome sequencing (WGS)-based method to characterize the capsule polysaccharide synthesis ( cps ) locus, classify N. meningitidis serogroups, and identify mechanisms for nongroupability using 453 isolates from a global strain collection. We identified novel genomic organizations within functional cps loci, consisting of insertion sequence (IS) elements in unique positions that did not disrupt the coding sequence. Genetic mutations (partial gene deletion, missing genes, IS insertion, internal stop, and phase-variable off) that led to nongroupability were identified. The results of WGS and SASG were in 91% to 100% agreement for all serogroups, while the results of WGS and RT-PCR showed 99% to 100% agreement. Among isolates determined to be nongroupable by WGS (31 of 453), the results of all three methods agreed 100% for those without a capsule polymerase gene. However, 61% (WGS versus SASG) and 36% (WGS versus RT-PCR) agreements were observed for the isolates, particularly those with phase variations or internal stops in cps loci, which warrant further characterization by additional tests. Our WGS-based serogrouping method provides comprehensive characterization of the N. meningitidis capsule, which is critical for meningococcal surveillance and outbreak investigations., (Copyright © 2019 American Society for Microbiology.)

In January and February 2015, Neisseria meningitidis serogroup B (NmB) outbreaks occurred at two universities in the United States, and mass vaccination campaigns using MenB vaccines were initiated as part of a public health response. Meningococcal carriage evaluations were conducted concurrently with vaccination campaigns at these two universities and at a third university, where no NmB outbreak occurred. Meningococcal isolates (N = 1,514) obtained from these evaluations were characterized for capsule biosynthesis by whole-genome sequencing (WGS). Functional capsule polysaccharide synthesis (cps) loci belonging to one of seven capsule genogroups (B, C, E, W, X, Y, and Z) were identified in 122 isolates (8.1%). Approximately half [732 (48.4%)] of isolates could not be genogrouped because of the lack of any serogroup-specific genes. The remaining 660 isolates (43.5%) contained serogroup-specific genes for genogroup B, C, E, W, X, Y, or Z, but had mutations in the cps loci. Identified mutations included frameshift or point mutations resulting in premature stop codons, missing or fragmented genes, or disruptions due to insertion elements. Despite these mutations, 49/660 isolates expressed capsule as observed with slide agglutination, whereas 45/122 isolates with functional cps loci did not express capsule. Neither the variable capsule expression nor the genetic variation in the cps locus was limited to a certain clonal complex, except for capsule null isolates (predominantly clonal complex 198). Most of the meningococcal carriage isolates collected from student populations at three US universities were non-groupable as a result of either being capsule null or containing mutations within the capsule locus. Several mutations inhibiting expression of the genes involved with the synthesis and transport of the capsule may be reversible, allowing the bacteria to switch between an encapsulated and non-encapsulated state. These findings are particularly important as carriage is an important component of the transmission cycle of the pathogen, and understanding the impact of genetic variations on the synthesis of capsule, a meningococcal vaccine target and an important virulence factor, may ultimately inform strategies for control and prevention of disease caused by this pathogen. [ABSTRACT FROM AUTHOR]