Meningococcal Surveillance Australia: Reporting period 1 April to 30 June 2023.

Abstract: The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and molecular based techniques. Data contained in quarterly reports are restricted to a description of case numbers of IMD by jurisdiction and serogroup, where known. A full analysis of laboratory confirmations of IMD in each calendar year are contained in the AMSP annual reports.

Meningococcal Surveillance Australia: Reporting period 1 July to 30 September 2023.

Abstract: The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and molecular based techniques. Data contained in quarterly reports are restricted to a description of case numbers of IMD by jurisdiction and serogroup, where known. A full analysis of laboratory confirmations of IMD in each calendar year are contained in the AMSP annual reports.

Meningococcal Surveillance Australia: Reporting period 1 October to 31 December 2023.

Abstract: The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and molecular based techniques. Data contained in quarterly reports are restricted to a description of case numbers of IMD by jurisdiction and serogroup, where known. A full analysis of laboratory confirmations of IMD in each calendar year are contained in the AMSP annual reports.

Recent increase in atypical presentations of invasive meningococcal disease in France.

BACKGROUND: Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical interventions (NPI) (social distancing and mask wearing) to control the COVID-19 pandemic but rebounded in 2022 in numbers with genotypical changes of the strains. We explored here associated modifications in the clinical presentations of IMD. METHODS: We conducted a retrospective descriptive study using the Database of the French National Reference Centre for meningococci and Haemophilus influnezae for IMD cases between 2015 and 2022. We scored serogroups, sex, age groups, clinical presentations and clonal complexes of the corresponding patients and isolates. FINDINGS: Non-meningeal forms of IMD increased significantly upon easing of NPI, such as bacteremic meningococcal pneumonia and bacteremic abdominal forms. They represented 6% and 8% of all IMD forms and were significantly linked to serogroups Y and W respectively, to older adults for bacteremic pneumonia and to young adults for bacteremic abdominal presentations. These forms were significantly associated with more early mortality and clonal complexes 23, 11 and 9316. INTERPRETATION: The increase in atypical IMD forms may lead to higher burden of IMD due to delayed diagnosis and management. Updating prevention may be needed through by adapting the current vaccination strategies to epidemiological changes.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

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).

Antibody persistence and revaccination recommendations of MenACWY-TT: a review of clinical studies assessing antibody persistence up to 10 years after vaccination.

INTRODUCTION: Invasive meningococcal disease (IMD) is potentially fatal and associated with severe sequelae among survivors. It is preventable by several vaccines, including meningococcal vaccines targeting the most common disease-causing serogroups (A, B, C, W, Y). The meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT [Nimenrix]) is indicated from 6 weeks of age in the European Union and >50 additional countries. AREAS COVERED: Using PubMed, Google Scholar, ClinicalTrials.gov and ad hoc searches for publications to June 2023, we review evidence of antibody persistence for up to 10 years after primary vaccination and up to 6 years after MenACWY-TT revaccination. We also review global MenACWY revaccination recommendations and real-world impact of vaccination policies, focusing on how these data can be considered alongside antibody persistence data to inform future IMD prevention strategies. EXPERT OPINION: Based on clear evidence that immunogenicity data (demonstrated antibody titers above established correlates of protection) are correlated with real-world effectiveness, long-term persistence of antibodies after MenACWY-TT vaccination suggests continuing protection against IMD. Optimal timing of primary and subsequent vaccinations is critical to maximize direct and indirect protection. Recommending bodies should carefully consider factors such as age at vaccination and long-term immune responses associated with the specific vaccine being used.

Prediction by genetic MATS of 4CMenB vaccine strain coverage of invasive meningococcal serogroup B isolates circulating in Taiwan between 2003 and 2020.

Neisseria meningitidis serogroup B (NmB) strains have diverse antigens, necessitating methods for predicting meningococcal serogroup B (MenB) vaccine strain coverage. The genetic Meningococcal Antigen Typing System (gMATS), a correlate of MATS estimates, predicts strain coverage by the 4-component MenB (4CMenB) vaccine in cultivable and non-cultivable NmB isolates. In Taiwan, 134 invasive, disease-causing NmB isolates were collected in 2003-2020 (23.1%, 4.5%, 5.2%, 29.8%, and 37.3% from individuals aged ≤11 months, 12-23 months, 2-4 years, 5-29 years, and ≥30 years, respectively). NmB isolates were characterized by whole-genome sequencing and vaccine antigen genotyping, and 4CMenB strain coverage was predicted using gMATS. Analysis of phylogenetic relationships with 502 global NmB genomes showed that most isolates belonged to three global hyperinvasive clonal complexes: ST-4821 (27.6%), ST-32 (23.9%), and ST-41/44 (14.9%). Predicted strain coverage by gMATS was 62.7%, with 27.6% isolates covered, 2.2% not covered, and 66.4% unpredictable by gMATS. Age group coverage point estimates ranged from 42.9% (2-4 years) to 66.1% (≤11 months). Antigen coverage estimates and percentages predicted as covered/not covered were highly variable, with higher estimates for isolates with one or more gMATS-positive antigens than for isolates positive for one 4CMenB antigen. In conclusion, this first study on NmB strain coverage by 4CMenB in Taiwan shows 62.7% coverage by gMATS, with predictable coverage for 29.8% of isolates. These could be underestimated since the gMATS calculation does not consider synergistic mechanisms associated with simultaneous antibody binding to multiple targets elicited by multicomponent vaccines or the contributions of minor outer membrane vesicle vaccine components.IMPORTANCEMeningococcal diseases, caused by the bacterium Neisseria meningitidis (meningococcus), include meningitis and septicemia. Although rare, invasive meningococcal disease is often severe and can be fatal. Nearly all cases are caused by six meningococcal serogroups (types), including meningococcal serogroup B. Vaccines are available against meningococcal serogroup B, but the antigens targeted by these vaccines have highly variable genetic features and expression levels, so the effectiveness of vaccination may vary depending on the strains circulating in particular countries. It is therefore important to test meningococcal serogroup B strains isolated from specific populations to estimate the percentage of bacterial strains that a vaccine can protect against (vaccine strain coverage). Meningococcal isolates were collected in Taiwan between 2003 and 2020, of which 134 were identified as serogroup B. We did further investigations on these isolates, including using a method (called gMATS) to predict vaccine strain coverage by the 4-component meningococcal serogroup B vaccine (4CMenB).

Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine.

Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy-treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.

Hybrid response to SARS-CoV-2 and Neisseria meningitidis C after an OMV-adjuvanted immunization in mice and their offspring.

COVID-19, caused by SARS-CoV-2, and meningococcal disease, caused by Neisseria meningitidis, are relevant infectious diseases, preventable through vaccination. Outer membrane vesicles (OMVs), released from Gram-negative bacteria, such as N. meningitidis, present adjuvant characteristics and may confer protection against meningococcal disease. Here, we evaluated in mice the humoral and cellular immune response to different doses of receptor binding domain (RBD) of SARS-CoV-2 adjuvanted by N. meningitidis C:2a:P1.5 OMVs and aluminum hydroxide, as a combined preparation for these pathogens. The immunization induced IgG antibodies of high avidity for RBD and OMVs, besides IgG that recognized the Omicron BA.2 variant of SARS-CoV-2 with intermediary avidity. Cellular immunity showed IFN-γ and IL-4 secretion in response to RBD and OMV stimuli, demonstrating immunologic memory and a mixed Th1/Th2 response. Offspring presented transferred IgG of similar levels and avidity as their mothers. Humoral immunity did not point to the superiority of any RBD dose, but the group immunized with a lower antigenic dose (0.5 µg) had the better cellular response. Overall, OMVs enhanced RBD immunogenicity and conferred an immune response directed to N. meningitidis too.

Mpox in children and adolescents and contact follow-up in school settings in greater Paris, France, May 2022 to July 2023.

BackgroundDuring the 2022 mpox outbreak in Europe, primarily affecting men who have sex with men, a limited number of cases among children and adolescents were identified. Paediatric cases from outbreaks in endemic countries have been associated with a higher likelihood of severe illness. Detailed clinical case descriptions and interventions in school settings before 2022 are limited.AimTo describe clinical characteristics of mpox cases among children (< 15 years) and adolescents (15-17 years) in the greater Paris area in France, and infection control measures in schools.MethodsWe describe all notified laboratory-confirmed and non-laboratory-confirmed cases among children and adolescents identified from May 2022 to July 2023, including demographic and clinical characterisation and infection control measures in school settings, i.e. contact tracing, contact vaccination, secondary attack rate and post-exposure vaccination uptake.ResultsNineteen cases were notified (13 children, 6 adolescents). Four adolescent cases reported sexual contact before symptom onset. Ten child cases were secondary cases of adult patients; three cases were cryptic, with vesicles on hands, arms and/or legs and one case additionally presented with genitoanal lesions. Five cases attended school during their infectious period, with 160 at-risk contacts identified, and one secondary case. Five at-risk contacts were vaccinated following exposure.ConclusionCases among children and adolescents are infrequent but require a careful approach to identify the source of infection and ensure infection control measures. We advocate a 'contact warning' strategy vs 'contact tracing' in order to prevent alarm and stigma. Low post-exposure vaccination rates are expected.

Interaction of Neisseria meningitidis carrier and disease isolates of MenB cc32 and MenW cc22 with epithelial cells of the nasopharyngeal barrier.

Neisseria meningitidis (Nm, the meningococcus) is considered an asymptomatic colonizer of the upper respiratory tract and a transient member of its microbiome. It is assumed that the spread of N. meningitidis into the bloodstream occurs via transcytosis of the nasopharyngeal epithelial barrier without destroying the barrier layer. Here, we used Calu-3 respiratory epithelial cells that were grown under air-liquid-interface conditions to induce formation of pseudostratified layers and mucus production. The number of bacterial localizations in the outer mucus, as well as cellular adhesion, invasion and transmigration of different carrier and disease N. meningitidis isolates belonging to MenB:cc32 and MenW:cc22 lineages was assessed. In addition, the effect on barrier integrity and cytokine release was determined. Our findings showed that all strains tested resided primarily in the outer mucus layer after 24 h of infection (>80%). Nonetheless, both MenB:cc32 and MenW:cc22 carrier and disease isolates reached the surface of the epithelial cells and overcame the barrier. Interestingly, we observed a significant difference in the number of bacteria transmigrating the epithelial cell barrier, with the representative disease isolates being more efficient to transmigrate compared to carrier isolates. This could be attributed to the capacity of the disease isolates to invade, however could not be assigned to expression of the outer membrane protein Opc. Moreover, we found that the representative meningococcal isolates tested in this study did not damage the epithelial barrier, as shown by TEER measurement, FITC-dextran permeability assays, and expression of cell-junction components.

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

Serogroup B Invasive Meningococcal Disease in Older Adults Identified by Genomic Surveillance, England, 2022-2023.

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

Analyzing the dynamics of meningococcal vaccinations initiatives by local government units in Poland (2017-2021) - Scope, challenges and recommendations.

INTRODUCTION: Meningococcal vaccinations are recommended by Polish public health authorities but lack coverage under health insurance, prompting Local Government Units (LGUs) to implement local health policy programs. This study examines the effectiveness and impact of LGU-driven meningococcal vaccination initiatives in Poland between 2017 and 2021. MATERIAL AND METHODS: A retrospective analysis utilized data from reports on local public health interventions submitted annually to the Ministry of Health in Poland. The study focused on the number of meningococcal vaccination programs, their scope, the vaccinated population, and associated program costs. Additionally, nationwide data on meningococcal disease incidence and vaccine uptake were analyzed. RESULTS: Within LGUs programs, 48,617 individuals received meningococcal vaccinations, constituting approximately 10% of all vaccinations in Poland during the study period. Notably, cities with poviat rights spearheaded programs covering 54% of the total participants. The total cost incurred by these initiatives amounted to EUR 2,553,661. CONCLUSIONS: While LGUs activities positively contributed to increased meningococcal vaccination rates, the overall engagement of local governments remains limited. The findings underscore the importance of expanding local government involvement in meningococcal vaccination programs to address public health needs effectively. Improved collaboration and increased funding may enhance the reach and impact of these initiatives.

Temporal variations in the serogroup distribution of invasive meningococcal disease in Quebec, Canada, due to emerging unique clade of serogroup Y strain belonging to the Sequence Type-23 clonal complex.

OBJECTIVE: To identify recent trends in invasive meningococcal diseases (IMD) in Quebec, Canada, with a focus on MenY cases and MenY strains. METHODS: IMD cases and MenY strains from January 1, 2015 to August 11, 2023 were analyzed for clonal analysis and prediction of susceptibility to MenB vaccines. MenY strains of ST-23 CC from Quebec were analyzed with global MenY strains by core-genomic multi-locus sequence typing (cg-MLST). RESULTS: Since 2015 the serogroup distribution of IMD in Quebec has shifted from predominantly MenB to mainly MenY, with most (80.9 %) of the latter belonging to ST-23 CC. The median age of MenY cases due to ST-23 CC were statistically younger than MenY cases due to non-ST-23 CC. MenY of ST-23 CC showed genetic diversity and the major genetic cluster were similar to the Swedish Y1 strain. The increase in invasive MenY disease in Quebec was due to a sub-clade of Lineage 23.1 which caused an elevated proportion of severe disease in young adults. CONCLUSION: The increase in invasive MenY disease in Quebec, Canada was driven by the expansion of a sub-clade of Lineage 23.1 in young adults. Currently available quadrivalent A,C,W,Y-conjugate meningococcal vaccines were predicted to provide protection against these strains.