Invasive meningococcal disease (IMD) is a severe illness that can have devastating effects; outbreaks are uncommon in the United States. Vaccination is the preferred control measure for IMD outbreaks when a defined population at risk (e.g., college students or persons experiencing homelessness) can be identified. In August 2022, the Virginia Department of Health (VDH) began investigating an IMD outbreak in Virginia's Eastern Health Planning Region, prompted by the detection of four confirmed cases within 8 weeks. Clinical isolates available from three cases were characterized as Neisseria meningitidis serogroup Y, sequence type 1466. A subsequent statewide investigation identified 36 genetically related cases, including seven deaths (case fatality rate = 19.4%) as of March 1, 2024. A majority of patients (63.9%) were in an age group (30-60 years) not generally considered at increased risk for IMD; 78.0% were non-Hispanic Black or African American. No common exposures, affiliations, or risk factors were identified, and a defined population could not be identified for vaccination. VDH recommended quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccination of a subset of close contacts of patients based on IMD risk factors and age range similar to that of patients with identified cases. IMD outbreaks might affect populations without established IMD risk factors. Lack of a well-defined population at risk might prompt exploration of novel control strategies, such as selective vaccination of close contacts.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

During January 28-May 5, 2019, a meningitis outbreak caused by Neisseria meningitidis serogroup C (NmC) occurred in Burkina Faso. Demographic and laboratory data for meningitis cases were collected through national case-based surveillance. Cerebrospinal fluid was collected and tested by culture and real-time PCR. Among 301 suspected cases reported in 6 districts, N. meningitidis was the primary pathogen detected; 103 cases were serogroup C and 13 were serogroup X. Whole-genome sequencing revealed that 18 cerebrospinal fluid specimens tested positive for NmC sequence type (ST) 10217 within clonal complex 10217, an ST responsible for large epidemics in Niger and Nigeria. Expansion of NmC ST10217 into Burkina Faso, continued NmC outbreaks in the meningitis belt of Africa since 2019, and ongoing circulation of N. meningitidis serogroup X in the region underscore the urgent need to use multivalent conjugate vaccines in regional mass vaccination campaigns to reduce further spread of those serogroups.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a sudden-onset, life-threatening illness that typically occurs as meningitis or meningococcemia. The most common signs and symptoms of meningitis include fever, headache, and stiff neck; the most common signs and symptoms of meningococcemia are fever, chills, fatigue, vomiting, diarrhea, cold hands and feet, and severe aches or pain.* Quadrivalent meningococcal conjugate vaccination (MenACWY) is routinely recommended for adolescents and persons at increased risk for meningococcal disease (1), including those with HIV. In 2016, a 2-dose series of MenACWY was recommended by the Advisory Committee on Immunization Practices (ACIP) for persons with HIV and incorporated into the U.S. immunization schedule. Coverage among persons with HIV, however, remains low: in a study of administrative claims data during January 2016–March 2018, only 16.3% of persons with HIV received ≥1 doses of MenACWY vaccine within 2 years after their diagnosis (2). This report describes an increase in meningococcal disease among persons with HIV in the United States in 2022. Data are typically finalized in the fall of the next year; therefore, this report is based on preliminary data for 2022.

To monitor the burden and changes in Haemophilus influenzae (Hi) disease, direct real-time PCR (drt-PCR) assays have been developed for Hi detection in monoplex form and its six serotypes in triplex form, directly from cerebrospinal fluid (CSF) specimens. These assays target the phoB gene for the species detection (Hi-phoB) and serotype-specific genes in region II of the capsule biosynthesis locus (Hi-abf and Hi-cde), identified through comparative analysis of Hi and non-Hi whole-genome sequences. The lower limit of detection (LLD) is 293 CFU/mL for the Hi-phoB assay and ranged from 11 to 130 CFU/mL for the triplex serotyping assays. Using culture as a reference method, the sensitivity and specificity of Hi-phoB, Hi-abf, and Hi-cde were 100%. Triplex serotyping assays also showed 100% agreement for each serotype compared to their corresponding monoplex serotyping assay. These highly sensitive and specific drt-PCR assays do not require DNA extraction and thereby reduce the time, cost, and handling required to process CSF specimens. Furthermore, triplex drt-PCR assays combine the detection of three serotypes in a single reaction, further improving testing efficiency, which is critical for laboratories that process high volumes of Hi specimens for surveillance and diagnostic purposes.

BACKGROUND: Penicillin and ciprofloxacin are important for invasive meningococcal disease (IMD) management and prevention. IMD cases caused by penicillin- and ciprofloxacin-resistant Neisseria meningitidis containing a ROB-1 β-lactamase gene (blaROB-1) and a mutated DNA gyrase gene (gyrA), have been recently reported in the USA. METHODS: We examined 2097 meningococcal genomes collected through US population-based surveillance from January 2011-February 2020 to identify IMD cases caused by strains with blaROB-1 or gyrA-mediated resistance. Antimicrobial resistance was confirmed phenotypically. The US isolate genomes were compared to non-US isolate genomes containing blaROB-1. Interspecies transfer of ciprofloxacin resistance was assessed by comparing gyrA among Neisseria species. RESULTS: Eleven penicillin- and ciprofloxacin-resistant isolates were identified after December 2018; all were serogroup Y, sequence type 3587, clonal complex (CC) 23, and contained blaROB-1 and a T91I-containing gyrA allele. An additional 22 penicillin-resistant, blaROB-1-containing US isolates with wild-type gyrA were identified from 2013-2020. All 33 blaROB-1-containing isolates formed a single clade, along with 12 blaROB-1-containing isolates from six other countries. Two-thirds of blaROB-1-containing US isolates were from Hispanic individuals. Twelve additional ciprofloxacin-resistant isolates with gyrA T91 mutations were identified. Ciprofloxacin-resistant isolates belonged to six CCs and contained 10 unique gyrA alleles; seven were similar or identical to alleles from N. lactamica or N. gonorrhoeae. CONCLUSIONS: Recent IMD cases caused by a dual resistant serogroup Y suggest changing antimicrobial resistance patterns in the USA. The emerging dual-resistance is due to acquisition of ciprofloxacin resistance by β-lactamase-containing N. meningitidis. Routine antimicrobial resistance surveillance will effectively monitor resistance changes and spread.

BACKGROUND: Microbial endocrinology, which is the study of neuroendocrine-based interkingdom signaling, provides a causal mechanistic framework for understanding the bi-directional crosstalk between the host and microbiome, especially as regards the effect of stress on health and disease. The importance of the cecal microbiome in avian health is well-recognized, yet little is understood regarding the mechanisms underpinning the avian host-microbiome relationship. Neuroendocrine plasticity of avian tissues that are focal points of host-microbiome interaction, such as the gut and lung, has likewise received limited attention. Avian in vivo models that enable the study of the neuroendocrine dynamic between host and microbiome are needed. As such, we utilized Japanese quail (Coturnix japonica) that diverge in corticosterone response to stress to examine the relationship between stress-related neurochemical concentrations at sites of host-microbe interaction, such as the gut, and the cecal microbiome. RESULTS: Our results demonstrate that birds which contrast in corticosterone response to stress show profound separation in cecal microbial community structure as well as exhibit differences in tissue neurochemical concentrations and structural morphologies of the gut. Changes in neurochemicals known to be affected by the microbiome were also identified in tissues outside of the gut, suggesting a potential relationship in birds between the cecal microbiome and overall avian physiology. CONCLUSIONS: The present study provides the first evidence that the structure of the avian cecal microbial community is shaped by selection pressure on the bird for neuroendocrine response to stress. Identification of unique region-dependent neurochemical changes in the intestinal tract following stress highlights environmental stressors as potential drivers of microbial endocrinology-based mechanisms of avian host-microbiome dialogue. Together, these results demonstrate that tissue neurochemical concentrations in the avian gut may be related to the cecal microbiome and reveal the Japanese quail as a novel avian model in which to further examine the mechanisms underpinning these relationships. Video abstract.

Effective laboratory-based surveillance and public health response to bacterial meningitis depends on timely characterization of bacterial meningitis pathogens. Traditionally, characterizing bacterial meningitis pathogens such as Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) required several biochemical and molecular tests. Whole genome sequencing (WGS) has enabled the development of pipelines capable of characterizing the given pathogen with equivalent results to many of the traditional tests. Here, we present the Bacterial Meningitis Genomic Analysis Platform (BMGAP): a secure, web-accessible informatics platform that facilitates automated analysis of WGS data in public health laboratories. BMGAP is a pipeline comprised of several components, including both widely used, open-source third-party software and customized analysis modules for the specific target pathogens. BMGAP performs de novo draft genome assembly and identifies the bacterial species by whole-genome comparisons against a curated reference collection of 17 focal species including Nm, Hi, and other closely related species. Genomes identified as Nm or Hi undergo multi-locus sequence typing (MLST) and capsule characterization. Further typing information is captured from Nm genomes, such as peptides for the vaccine antigens FHbp, NadA, and NhbA. Assembled genomes are retained in the BMGAP database, serving as a repository for genomic comparisons. BMGAP's species identification and capsule characterization modules were validated using PCR and slide agglutination from 446 bacterial invasive isolates (273 Nm from nine different serogroups, 150 Hi from seven different serotypes, and 23 from nine other species) collected from 2017 to 2019 through surveillance programs. Among the validation isolates, BMGAP correctly identified the species for all 440 isolates (100% sensitivity and specificity) and accurately characterized all Nm serogroups (99% sensitivity and 98% specificity) and Hi serotypes (100% sensitivity and specificity). BMGAP provides an automated, multi-species analysis pipeline that can be extended to include additional analysis modules as needed. This provides easy-to-interpret and validated Nm and Hi genome analysis capacity to public health laboratories and collaborators. As the BMGAP database accumulates more genomic data, it grows as a valuable resource for rapid comparative genomic analyses during outbreak investigations.