The quality-adjusted life-years loss due to serogroup B invasive meningococcal disease in Spain.

INTRODUCTION: Despite its impact on a patient's life, there is a paucity of evidence on the humanistic burden of invasive meningococcal disease (IMD) due to serogroup B (MenB) in Spain. This study estimates the total quality-adjusted life-year (QALY) loss due to MenB-IMD in Spain from a societal perspective. MATERIALS AND METHODS: A previously published incidence-based Excel tool adapted to the Spanish setting was used to estimate total QALY losses over a patient's lifetime horizon, including direct and indirect impact on patients and families/caregivers, respectively. A 3% discount rate was applied, and a deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty and assumptions used for the base case. RESULTS: The total discounted QALY loss for a hypothetical cohort of 142 cases of MenB-IMD was 572.44 QALYs (4.03/case). Direct loss (attributable to patients) represented 81.2% of the total loss (464.54 QALYs; 3.27/case) and indirect loss (caused to relatives/ caregivers) represented 18.8% (108.90 QALYs; 0.76/case). Sequelae had the highest impact on QALY loss for both patients (60.5%) and relatives/caregivers (84.6%). Children <5 years of age (YOA) accounted for 47.8% of the total QALY loss. Mortality accounted for 17.62 QALY loss per death. The discount rate parameter showed the highest influence on results and the probabilistic sensitivity analysis revealed a 98.0% probability of total QALY loss achieving the point estimate. CONCLUSIONS: The results emphasize that the humanistic burden associated with a MenB case is mainly driven by its sequelae, impacting the patients and their relatives/caregivers.

Young Adult and Parent Willingness to Pay for Meningococcal Serogroup B Vaccination.

Introduction. Serogroup B (MenB) is the leading cause of invasive meningococcal disease among adolescents and young adults in the United States. The US Advisory Committee on Immunization Practices (ACIP) recommends MenB vaccination based on shared clinical decision making between patients and providers. However, suboptimal understanding of these recommendations could contribute to low vaccination awareness and coverage. Understanding young adult and parent expectations of their health care providers (HCPs) and the value they place on vaccine information could help inform a consistent approach to HCP MenB vaccination discussions and recommendations. Methods. Data collected via a discrete-choice experiment online survey were used to evaluate preferences and willingness to pay regarding MenB vaccination among US parents and young adults in 2019. Results. Of 2,388 respondents with valid data, 1,185 were parents of children aged 12 to 25 y, and 1,203 were young adults aged 18 to 25 y. Approximately 70% of parents and young adults indicated that they would react negatively if their HCP chose not to initiate a discussion with them about MenB vaccines. Neither parents nor young adults were willing to pay for additional time for MenB vaccine discussions with their HCP but were willing to pay an average of $416 and $282, respectively, for the vaccine. For parents and young adults, greater willingness to pay was associated with a provaccination attitude and the opinion that the HCP has a moral obligation to discuss the MenB vaccine with them. Conclusion. Both parents and young adults felt their HCP is responsible for initiating a discussion about MenB vaccination and disease risk and were willing to pay for the vaccine. These findings should help inform ACIP recommendations for meningococcal vaccination. Highlights: ACIP recommends shared clinical decision making for MenB vaccination.Data were collected from young adults and parents of adolescents by online survey.We measured values and consultation preferences on MenB disease and vaccination.Young adults/parents strongly preferred doctor-initiated MenB vaccine discussion.Respondents were willing to pay for a MenB vaccine.

Public health management of invasive meningococcal disease outbreaks: worldwide 1973-2018, a systematic review.

BACKGROUND: Infectious disease outbreaks are an ongoing public health concern, requiring extensive resources to prevent and manage. Invasive Meningococcal Disease (IMD) is a severe outcome of infection with Neisseria meningitidis bacteria, which can be carried and transmitted asymptomatically. IMD is not completely vaccine-preventable, presenting an ongoing risk of outbreak development. This review provides a retrospective assessment of public health management of IMD outbreaks. METHODS: A systematic search was performed in PubMed and EMBASE. English-language studies reporting on IMD outbreaks and associated public health response were considered eligible. Reporting on key characteristics including outbreak size, duration, location, and public health response were assessed against Strengthening the Reporting of Observational studies in Epidemiology guidelines. A summary of lessons learned and author recommendations for each article were also discussed. RESULTS: 39 eligible studies were identified, describing 35 outbreaks in seven regions. Responses to outbreaks were mostly reactive, involving whole communities over prioritising those at highest risk of transmission. Recent responses identified a need for more proactive and targeted controls. Reporting was inconsistent, with key characteristics such as outbreak size, duration, or response absent or incompletely described. CONCLUSION: There is a need for clear, comprehensive reporting on IMD outbreaks and their public health response to inform policy and practice for subsequent outbreaks of IMD and other infectious diseases.

Genetic characterization and estimated 4CMenB vaccine strain coverage of 284 Neisseria meningitidis isolates causing invasive meningococcal disease in Argentina in 2010-2014.

Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.

The most common clinical manifestations of invasive meningococcal disease include meningitis and septicemia, which can be deadly, and many survivors suffer long-term serious after-effects. Most cases of invasive meningococcal disease are caused by six meningococcal serogroups (types), including serogroup B. Although vaccines are available against meningococcal serogroup B infection, these vaccines target antigens that are highly diverse. Consequently, the effectiveness of vaccination may vary from country to country because the meningococcal serogroup B strains circulating in particular regions carry different forms of the target vaccine antigens. This means it is important to test serogroup B strains isolated from specific populations to estimate the percentage of strains that a vaccine is likely to be effective against (known as 'vaccine strain coverage'). The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict strain coverage by the four-component meningococcal serogroup B vaccine, 4CMenB, against large numbers of serogroup B strains. In this study, we analyzed 284 invasive meningococcal serogroup B isolates collected between 2010 and 2014 in Argentina. Genetic analyses showed that the vaccine antigens of the isolates were diverse and some genetic characteristics had not been found in isolates from other countries. However, vaccine strain coverage estimated by gMATS was consistent with that reported in other parts of the world and with strain coverage results obtained for a subset via another method, the human serum bactericidal antibody (hSBA) assay. These results highlight the need for continued monitoring of circulating bacterial strains to assess the estimated strain coverage of meningococcal serogroup B vaccines.

The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Vaccine effectiveness and impact of meningococcal vaccines against gonococcal infections: A systematic review and meta-analysis.

OBJECTIVES: To systematically review and synthesis the evidence of vaccine effectiveness (VE) and impact (VI) of meningococcal vaccines in preventing gonorrhoea. METHODS: We systematically evaluated studies. Literature searches were conducted in PubMed, Embase, Cochrane Library, CINAHL, Google Scholar, clinical trial registries, and major health and immunisation conferences. Meta-analysis was performed with the DerSimonian-Laird random-effects model to estimate the pooled VE. RESULTS: Twelve studies met the criteria for inclusion. VE of meningococcal B (MenB) outer membrane vesicle (OMV) vaccines was evaluated in nine studies, with one study evaluating a non-OMV vaccine, MenB-FHbp. The majority of studies targeted individuals aged 15-30 years. Adjusted VE for OMV vaccines against gonorrhoea ranged from 22% to 46%. MenB-FHbp did not show protection against gonorrhoea. The pooled VE estimates of OMV vaccines against any gonorrhoea infection following the full vaccine series were 33-34%. VI was assessed for 4CMenB in Canada and Australia, for VA-MENGOC-BC in Cuba; and for MenBvac in Norway. VI ranged from a 30% to 59% reduction in gonorrhoea incidence. CONCLUSIONS: 4CMenB and other MenB-OMV vaccines show moderate effectiveness against gonorrhoea. Further research is required to explore the factors associated with vaccine protection, informing more effective vaccination strategies for the management of gonococcal infections.

Effectiveness and duration of protection of primary and booster immunisation against meningococcal serogroup C disease with meningococcal conjugate C and ACWY vaccines: Systematic review.

OBJECTIVES: To estimate vaccine effectiveness (VE) and duration of protection of single primary and booster immunisation with meningococcal C (MenC) and ACWY (MenACWY) conjugate vaccines in preventing MenC invasive meningococcal disease (IMD). METHODS: We performed a systematic review on studies of VE and immunogenicity (rSBA/hSBA titers) of participants aged 12-23 months for primary and 6-18 years for booster immunisation (last search: 18 August 2023). Risk of bias and certainty of evidence were evaluated (PROSPERO: CRD42020178773). RESULTS: We identified 10 studies. Two studies reported VE of primary immunisation with MenC vaccines ranging between 90% (74.9 - 96.1) and 84.1% (41.5 - 95.7) for periods of 2 and 7 years, respectively. Eight studies reported immunogenicity of primary immunisation with MenC and/or MenACWY vaccines, of which two reported -in addition- on booster immunisation. The percentage of participants with protective rSBA titers was high after primary immunisation but waned over the following 6 years. A single booster at the age of 7 years or older seems to prolong protection for several years. CONCLUSIONS: A single dose of MenC or MenACWY vaccine at 12-23 months of age provides robust protection against MenC IMD. Data on booster immunisation are sparse, but indicate prolonged protection for three years at least.

Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine Versus Nimenrix in Healthy Adolescents: A Randomized Phase IIIb Multicenter Study.

INTRODUCTION: Many immunization programs in Europe recommend quadrivalent meningococcal vaccinations, which are often administered concomitantly with other vaccines. We compared the immune response of a tetanus toxoid conjugated quadrivalent meningococcal vaccine (MenACYW-TT, MenQuadfi®) with another quadrivalent meningococcal conjugate vaccine (MCV4-TT; Nimenrix®) when administered alone or concomitantly with Tdap-IPV and 9vHPV vaccines in adolescents. METHODS: In this phase IIIb trial, healthy adolescents (MenC-naïve or MenC-primed before 2 years of age) from Spain, Italy, Hungary, and Singapore were randomized in a 3:3:2 ratio to receive either MenACYW-TT or MCV4-TT alone, or MenACYW-TT concomitantly with 9vHPV and Tdap-IPV. The primary objective was to demonstrate the non-inferiority of the seroprotection rate (human serum bactericidal assay [hSBA] titer ≥ 1:8) to serogroups A, C, W, and Y 30 days post-vaccination with a single dose of MenACYW-TT or MCV4-TT. Secondary objectives included describing hSBA titers for the four serogroups before and 1 month following vaccination and according to MenC priming status. RESULTS: A total of 463 participants were enrolled (MenACYW-TT, n = 173; MCV4-TT, n = 173; MenACYW-TT/9vHPV/Tdap-IPV n = 117). Non-inferiority based on seroprotection was demonstrated for MenACYW-TT versus MCV4-TT for all serogroups. Immune responses were comparable whether MenACYW-TT was administered alone or concomitantly with Tdap-IPV and 9vHPV. Post-vaccination hSBA GMTs were higher in MenACYW-TT vs. MCV4-TT for serogroups C, Y, and W and comparable for serogroup A. The percentages of participants with an hSBA vaccine seroresponse were higher in MenACYW-TT vs. MCV4-TT for all serogroups. For serogroup C, higher GMTs were observed in both MenC-naïve or -primed participants vaccinated with MenACYW-TT vs. MCV4-TT. Seroprotection and seroresponse were higher in MenC-naïve participants vaccinated with MenACYW-TT vs. MCV4-TT and comparable in MenC-primed. The safety profiles were comparable between groups and no new safety concerns were identified. CONCLUSIONS: These data support the concomitant administration of MenACYW-TT with 9vHPV and Tdap-IPV vaccines in adolescents. TRIAL REGISTRATIONS: Clinicaltrials.gov, NCT04490018; EudraCT: 2020-001665-37; WHO: U1111-1249-2973.

MenACYW conjugate vaccine has been made to protect against meningococcal disease caused by four common types of bacteria (germs) called Neisseria meningitidis (or meningococcus), A, C, W, and Y. Many people, particularly adolescents, have the germs of this disease in their nose or throat, and therefore may develop the disease or transmit the bacteria to other people. Hence, adolescent meningococcal vaccination against serogroups ACWY is increasingly recommended in several countries. This study assessed the immune response to these serogroups in healthy adolescents after one dose of MenACYW conjugate vaccine or Nimenrix^®, a meningococcal licensed vaccine. Moreover, the immune response and safety were assessed when the vaccines were given alone or when given concomitantly with other adolescent vaccines, including the human papillomavirus (9vHPV) and tetanus, diphtheria, pertussis, and poliomyelitis (Tdap-IPV) vaccines. A total of 463 adolescents (aged 10­17 years) participated in this study and received either MenACYW or Nimenrix^® alone, or MenACYW concomitantly with 9vHPV and Tdap-IPV vaccine. The immune response induced by MenACYW was as good as the immune response induced by Nimenrix^®, and when given alone or concomitantly with 9vHPV and Tdap IPV vaccines. None of the participants experienced any serious side effects of any vaccine. The most common non-serious side effects were injection site pain, muscle pain, and headache. These data support the use of MenACYW in adolescents, with or without concomitant administration with 9vHPV and Tdap-IPV, which may help to increase the number of adolescents vaccinated.

Quantifying Stated Preferences for Meningococcal Vaccines Among Adolescents/Young Adults and Parents of Adolescents in the United States: A Discrete Choice Experiment.

INTRODUCTION: Invasive meningococcal disease (IMD) is a severe and life-threatening disease. In the United States (US), vaccine coverage with MenACWY and MenB meningococcal vaccines is suboptimal among adolescents/young adults aged 16-23 years. A combined meningococcal vaccine (MenABCWY) could increase convenience (e.g., fewer injections) and improve coverage. The objective was to quantify preferences for hypothetical meningococcal vaccine profiles among adolescents/young adults and parents. METHODS: An online discrete choice experiment was conducted among 16- to 23-year-olds, and parents of 16- to 18-year-olds. Attributes (3 × 4) and levels (1 × 2) were based on the literature and focus groups. Participants made ten pair-wise forced trade-off choices, systematically varied using a D-optimal design. Random parameter logit quantified the relative importance of vaccination attributes and estimated the trade-offs. Differences in preferences by subgroups were assessed. RESULTS: Totals of 300 adolescents and young adults (median age 20 years) and 300 parents (median age 46 years) completed the survey. Overall, 89.6% of 16- to 23-year-olds and 69.1% of parents preferred a simplified hypothetical meningococcal vaccination profile, e.g., with fewer injections (3 vs. 4) and fewer healthcare provider (HCP) visits (2-3 vs. 4). Having HCP advice and clear Centers for Disease Control and Prevention recommendations impacted vaccination choice, with both groups reporting high trust in HCP information (83.3% among 16- to 23-year-olds; 98.7% among parents). Barriers to vaccination included lack of HCP advice or awareness of meningococcal vaccines, and income level and out-of-pocket costs for parents. CONCLUSIONS: Adolescents/young adults and parents demonstrated a significant preference for a meningococcal vaccine that is more convenient (such as combined MenABCWY). Parents' vaccination preferences differed by income level and out-of-pocket costs, suggesting financial barriers to vaccination may exist which could result in IMD prevention inequalities. Findings from this study provide important information to support patient-facing informed policy discussions. A simplified vaccination schedule and strong recommendation could help improve vaccine uptake, schedule compliance, disease prevention, and reduce inequalities in IMD risk and prevention. A graphical abstract is available with this article.

Exploring meningococcal serogroup B vaccination conversations under shared clinical decision-making in the US.

OBJECTIVE: In 2019, the United States Advisory Committee on Immunization Practices (ACIP) updated their meningococcal serogroup B (MenB) vaccination recommendation for 16-|23-year-olds from individual to shared clinical decision-making (SCDM). SCDM recommendations are individually based and informed by a decision process between patients and healthcare providers (HCPs). MenB vaccination among 16-23-year-olds remains low. We examined recorded conversations in which MenB vaccine-related discussions between HCPs and patients/caregivers took place, and how these interactions changed following the updated SCDM recommendation. METHODS: An analysis of recordings where MenB vaccination was discussed between HCPs and patients (16-|23 years old)/caregivers was conducted using retrospective anonymized dialogue data (January 2015-October 2022). Shared decision-making strength was measured using a modified OPTION5 framework. RESULTS: Of 97 included recorded conversations, the average duration was 11.3 min. Within these conversations, MenB disease was discussed for 0.25 min (38.9% of words in total vaccine-preventable diseases discussion) and MenB vaccination was discussed for 1.36 min (60.9% of words in total vaccine discussion), on average. HCPs spoke 78.8% of MenB vaccine-related words and most (99.0%) initiated the MenB vaccination discussion. In 40.2% of recordings, HCPs acknowledged the MenB vaccine without providing a clear recommendation. HCP recommendations often favored MenB vaccination (87.0%) and recommendations were 21.4% stronger post-recommendation change to SCDM. As measured by the modified OPTION5 framework, most recordings did not reflect a high degree of shared decision-making between HCPs and patients/caregivers. CONCLUSIONS: MenB vaccination discussions were brief, and the degree of shared decision-making was low. Targeted education of HCPs and patients/caregivers may improve MenB vaccination awareness, SCDM implementation, and vaccine uptake.

Meningitis is a serious and sometimes deadly disease. In the United States (US), the Centers for Disease Control and Prevention (CDC) recommends that 16­23-year-olds get vaccinated against meningococcal serogroup B (MenB), which causes a specific type of meningitis called invasive meningococcal disease. As of 2019, the CDC recommends that healthcare providers and patients or their caregivers have a shared decision-making discussion about deciding to get vaccinated against MenB. Despite these recommendations, vaccination against MenB among 16­23-year-olds is very low. Only about 3 in 10 17-year-olds had received the MenB vaccine in 2022. We studied conversations between healthcare providers and patients or their caregivers that included discussions of MenB vaccination. These discussions were largely brief and led by the healthcare providers. We found that healthcare providers most often made recommendations that were in favor of their patients getting vaccinated against MenB. However, we also found that healthcare providers missed many opportunities to have these shared decision-making discussions about MenB vaccination with patients or their caregivers. Providing education and resources for patients, caregivers, and healthcare providers focused on increasing awareness about MenB vaccination and the role they can play in having shared decision-making discussions may lead to more adolescents and young adults getting vaccinated against MenB. More research is needed to find out how we can improve MenB vaccination coverage in the US.

Effectiveness of quadrivalent meningococcal conjugate vaccine against meningococcal carriage and genotype character changes: A secondary analysis of prospective cohort study in Korean military trainees.

OBJECTIVE: We evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. METHODS: Oropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). RESULTS: Of 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P = 0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95% CI: 36.3-88.2), and serogroup C was particularly reduced (VEC = 83.0%, 95% CI: 50.6-94.1), whereas non-groupable isolates increased significantly after vaccination (VENG = -76.1%, 95% CI: -176.2 to -13.1). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. CONCLUSIONS: MenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.

Developing a Novel Murine Meningococcal Meningitis Model Using a Capsule-Null Bacterial Strain.

BACKGROUND: Neisseria meningitidis (meningococcus) is a Gram-negative bacterium that colonises the nasopharynx of about 10% of the healthy human population. Under certain conditions, it spreads into the body, causing infections with high morbidity and mortality rates. Although the capsule is the key virulence factor, unencapsulated strains have proved to possess significant clinical implications as well. Meningococcal meningitis is a primarily human infection, with limited animal models that are dependent on a variety of parameters such as bacterial virulence and mouse strain. In this study, we aimed to develop a murine Neisseria meningitidis meningitis model to be used in the study of various antimicrobial compounds. METHOD: We used a capsule-deficient Neisseria meningitidis strain that was thoroughly analysed through various methods. The bacterial strain was incubated for 48 h in brain-heart infusion (BHI) broth before being concentrated and injected intracisternally to bypass the blood-brain barrier in CD-1 mice. This prolonged incubation time was a key factor in increasing the virulence of the bacterial strain. A total of three more differently prepared inoculums were tested to further solidify the importance of the protocol (a 24-h incubated inoculum, a diluted inoculum, and an inactivated inoculum). Antibiotic treatment groups were also established. The clinical parameters and number of deaths were recorded over a period of 5 days, and comatose mice with no chance of recovery were euthanised. RESULTS: The bacterial strain was confirmed to have no capsule but was found to harbour a total of 56 genes coding virulence factors, and its antibiotic susceptibility was established. Meningitis was confirmed through positive tissue culture and histological evaluation, where specific lesions were observed, such as perivascular sheaths with inflammatory infiltrate. In the treatment groups, survival rates were significantly higher (up to 81.25% in one of the treatment groups compared to 18.75% in the control group). CONCLUSION: We managed to successfully develop a cost-efficient murine (using simple CD-1 mice instead of expensive transgenic mice) meningococcal meningitis model using an unencapsulated strain with a novel method of preparation.

A phase 3 non-inferiority trial of locally manufactured Meningococcal ACWY vaccine 'Ingovax ACWY' among Bangladeshi adults.

Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri MeningoTM (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri MeningoTM vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh.

Genomic Surveillance of Invasive Meningococcal Disease During a National MenW Outbreak in Australia, 2017-2018.

Background: In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data. Methods: Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms. Results: Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia. Conclusions: Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia.

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.

Spatio-temporal pattern and associate meteorological factors of airborne diseases in Bangladesh using geospatial mapping and spatial regression model.

Background and Aims: Airborne diseases due to climate change pose significant public health challenges in Bangladesh. Little was known about the spatio-temporal pattern of airborne diseases at the district level in the country. Therefore, this study aimed to investigate the spatio-temporal pattern and associated meteorological factors of airborne diseases in Bangladesh using exploratory analysis and spatial regression models. Methods: This study used district-level reported cases of airborne diseases (meningococcal, measles, mumps, influenza, tuberculosis, and encephalitis) and meteorological data (temperature, relative humidity, wind speed, and precipitation) from 2017 to 2020. Geospatial mapping and spatial error regression models were utilized to analyze the data. Results: From 2017 to 2020, a total of 315 meningococcal, 5159 measles, 1341 mumps, 346 influenza, 4664 tuberculosis, and 229 encephalitis cases were reported in Bangladesh. Among airborne diseases, measles demonstrated the highest prevalence, featuring a higher incidence rate in the coastal Bangladeshi districts of Lakshmipur, Patuakhali, and Cox's Bazar, as well as in Maulvibazar and Bandarban districts from 2017 to 2020. In contrast, tuberculosis (TB) emerged as the second most prevalent disease, with a higher incidence rate observed in districts such as Khagrachhari, Rajshahi, Tangail, Bogra, and Sherpur. The spatial error regression model revealed that among climate variables, mean (ß = 9.56, standard error [SE]: 3.48) and maximum temperature (ß = 1.19, SE: 0.40) were significant risk factors for airborne diseases in Bangladesh. Maximum temperature positively influenced measles (ß = 2.74, SE: 1.39), whereas mean temperature positively influenced both meningococcal (ß = 5.57, SE: 2.50) and mumps (ß = 11.99, SE: 3.13) diseases. Conclusion: The findings from the study provide insights for planning early warning, prevention, and control strategies to combat airborne diseases in Bangladesh and similar endemic countries. Preventive measures and enhanced monitoring should be taken in some high-risk districts for airborne diseases in the country.

Exploring the Health-Related Quality of Life and the Lived Experience of Adolescents Following Invasive Meningococcal Disease.

BACKGROUND: Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs. METHODS: Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically. RESULTS: Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge. CONCLUSION: The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.

Evaluation of antibody responses in healthcare workers before & after meningococcal vaccine and determination of meningococcal carriage rates.

The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not included in risk groups for many countries. Herein, we aimed to investigate the nasopharyngeal meningococcal carriage rates, basal and after one dose of Men-ACWY-DT vaccine response on the 30th day by evaluating meningococcus IgG antibody levels and decolonization at month six after vaccination among the detected carriers. Nasopharyngeal swab samples were taken before vaccination to evaluate meningococcal carriage in healthcare workers. All participants received a single dose of Men-ACWY-DT vaccine. Serum samples were collected immediately before vaccination and again on day 30 post-vaccination. Antibodies in the stored sera were analyzed using the ELISA method. Participants who were determined to carry meningococci at the initial visit underwent another round of nasopharyngeal swab tests six months post-vaccination to check for decolonization. Between November 2020 and May 2021, we evaluated samples from 100 physicians [52 % females, 28.28 ± 4.45 (min: 24, max: 49)]. The majority of the physicians worked in the emergency department (45 %), followed by the infectious diseases clinic (14 %). Fifty-eight physicians had a history of at least one contact with a meningococcus-infected patient, and 53 (91.4 %) had used prophylactic antibiotics at least once due to this exposure. None of the study group nasopharyngeal swab cultures were positive for Neisseria meningitidis. Before the Men-ACWY-DT vaccine, anti-meningococcus IgG positivity was detected in the serum samples of only 3 (3 %) participants. By day 30 after vaccination, 48 % of participants showed positive for antibodies. As we didn't detect nasopharyngeal carriage in any participants, we didn't evaluate decolonization among carriers six months post-vaccination. Notably, detection of antibodies was evident in about half of the participants on day 30 after receiving a single dose of the Men-ACWY-DT vaccine.

Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Thrombosis and meningococcal infection rates in pegcetacoplan-treated patients with paroxysmal nocturnal hemoglobinuria in the clinical trial and postmarketing settings.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening Neisseria infections, especially N meningitidis, represents a long-term safety risk of complement inhibition. Objectives: To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan. Methods: Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against Streptococcus pneumoniae, N meningitidis, and Haemophilus influenzae before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination. Results: As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported. Conclusion: Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required.