Meningococcal Research Articles

What Works for Controlling Meningitis Outbreaks: A Case Study from China.

The meningococcal meningitis (MM) vaccine reduces the incidence of MM significantly; however, outbreaks still occur in communities with high vaccine coverage. We aimed to analyze the driving factors of infection from a community outbreak. A total of 266 children aged 9 to 15 years old from the three junior high schools of Tongzi county were identified. We documented infection cases using laboratory tests and analyzed attack rates, infection rates and risk factors for transmission. The index case in School A was identified, and the attack rate in School A was 0.03%. Children showed a significantly low infection rate of MenC in School A (13.2% vs. 19.5% in total children, p = 0.002), while exhibiting significantly high infection rates of MenA in School B (44.1% vs. 24.8% in total children, p < 0.001) and MenB in School C (11.1% vs. 4.1% in total children, p = 0.015). The infection rate of MenA for females (30.0%) was higher (p = 0.055) than for males (19.9%). In School A, 63.19% of children were vaccinated against MenC, while in School B the rate was 42.65% and in School C, it was 59.26%. Three male MenC infection cases were detected as breakthrough infection cases in addition to the index case. The findings suggest that the current full-course immunization has limited long-term effectiveness and is inefficient in preventing the transmission of MM among older children.

Modular bioengineering of whole-cell catalysis for sialo-oligosaccharide production: coordinated co-expression of CMP-sialic acid synthetase and sialyltransferase

BackgroundIn whole-cell bio-catalysis, the biosystems engineering paradigm shifts from the global reconfiguration of cellular metabolism as in fermentation to a more focused, and more easily modularized, optimization of comparably short cascade reactions. Human milk oligosaccharides (HMO) constitute an important field for the synthetic application of cascade bio-catalysis in resting or non-living cells. Here, we analyzed the central catalytic module for synthesis of HMO-type sialo-oligosaccharides, comprised of CMP-sialic acid synthetase (CSS) and sialyltransferase (SiaT), with the specific aim of coordinated enzyme co-expression in E. coli for reaction flux optimization in whole cell conversions producing 3′-sialyllactose (3SL).ResultsDifference in enzyme specific activity (CSS from Neisseria meningitidis: 36 U/mg; α2,3-SiaT from Pasteurella dagmatis: 5.7 U/mg) was compensated by differential protein co-expression from tailored plasmid constructs, giving balance between the individual activities at a high level of both (α2,3-SiaT: 9.4 × 102 U/g cell dry mass; CSS: 3.4 × 102 U/g cell dry mass). Finally, plasmid selection was guided by kinetic modeling of the coupled CSS-SiaT reactions in combination with comprehensive analytical tracking of the multistep conversion (lactose, N-acetyl neuraminic acid (Neu5Ac), cytidine 5′-triphosphate; each up to 100 mM). The half-life of SiaT in permeabilized cells (≤ 4 h) determined the efficiency of 3SL production at 37 °C. Reaction at 25 °C gave 3SL (40 ± 4 g/L) in ∼ 70% yield within 3 h, reaching a cell dry mass-specific productivity of ∼ 3 g/(g h) and avoiding intermediary CMP-Neu5Ac accumulation.ConclusionsCollectively, balanced co-expression of CSS and SiaT yields an efficient (high-flux) sialylation module to support flexible development of E. coli whole-cell catalysts for sialo-oligosaccharide production.

1146. Cost-effectiveness of the Pentavalent Meningococcal Vaccine (MenABCWY): A steady-state cohort modelling approach

Abstract Background Invasive meningococcal disease (IMD) is associated with a high case fatality rate and serious long-term sequelae (LTS). The current US vaccination platform targets serogroups ACWY with a routine recommendation in adolescents (11-12 years, with a booster at 16 years) and serogroup B (16-23 years) based on shared clinical decision making. A novel pentavalent meningococcal vaccine (MenABCWY) may improve protection against all five serogroups and simplify vaccination schedule. The study objective was to assess the cost-effectiveness of MenABCWY from a societal perspective in the US. Methods A steady-state model was developed to estimate the impact of various vaccination strategies on IMD cases, LTS, and deaths. Cohorts of 11- and 16-year-olds were simulated over a lifetime (up to 100 years of age) after vaccination. The same vaccine uptake rate was applied to all strategies. Costs included vaccination acquisition and administration, and IMD direct and indirect costs. Disutilities of IMD and LTS were applied to estimate losses of quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated as the difference in costs over QALY gained comparing a strategy of implementing the MenABCWY vaccine with the current standard of care (SoC). Extensive scenario analyses were conducted. Results In the base case, compared with the SoC (one dose of a MenACWY vaccine at 11 years with a booster at 16 years, and two doses of a MenB vaccine at 16 years), introducing two doses of the MenABCWY vaccine at 11 years followed by a booster at 16 years (2+1 schedule) would prevent 63 IMD cases, 17 IMD cases with LTS, and 6 IMD-related deaths while providing savings (dominant ICERs). Results on ICERs, IMD cases, and IMD-related deaths were robust in scenario analyses when inputs most likely to influence the public health impact (i.e., IMD incidence and case fatality rate) were modified over plausible ranges. Conclusion The MenABCWY vaccine fits the current vaccination platform. Results of the cost-effectiveness analysis demonstrate that the 2+1 schedule could offer the most public health benefits by providing the full protection against all five serogroups at an early age, while being a dominant economic strategy. Disclosures Katharina Schley, Dr., Pfizer Pharma GmbH: Employee|Pfizer Pharma GmbH: Employee|Pfizer Pharma GmbH: Stocks/Bonds|Pfizer Pharma GmbH: Stocks/Bonds Jessica V. Presa, MD, Pfizer Inc.: Stocks/Bonds|Pfizer Inc.: Stocks/Bonds Vincenza Snow, MD, Pfizer Vaccines: employee|Pfizer Vaccines: Stocks/Bonds Alejandro D. Cane, MD, PhD, Pfizer: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds Ray Farkouh, PhD, Pfizer: Stocks/Bonds Shannon M. Sullivan, PhD, Evidera: I am an employee of Evidera that is a consultancy to multiple pharma companies|Pfizer: Advisor/Consultant Hossein Zivaripiran, PhD, Pfizer: Advisor/Consultant|Pfizer: I am an employee of Evidera that is a consultancy to multiple pharma companies Diana Teloian, MA, Merck &amp; Co., Inc: Grant/Research Support Jörgen Möller, MSc, Evidera: I am an employee of Evidera that is a consultancy to multiple pharma companies|Pfizer: Advisor/Consultant J. Jaime Caro, MDCM, FRCPC, FACP, Evidera: I am an employee of Evidera, a consultancy serving the pharmaceutical industry.|Pfizer: Advisor/Consultant

1137. The Value of Invasive Meningococcal Disease Combination Vaccine – a Qualitative Study of Adolescents and Parents/Caregivers’ Preferences in the US

Abstract Background MenACWY and MenB are commonly used vaccines to prevent invasive meningococcal disease (IMD), targeting serogroups A, B, C, W, Y. MenABCWY combination vaccines are under development and could provide increased vaccine coverage of serogroups. This qualitative study aimed to identify concepts affecting preferences in adolescents (Ado) and parents/caregivers (P/C) decision making towards combination vaccine in the US. Methods Two focus group discussions (FGD), 90-minutes with Ado (16-23 years) and P/C of adolescents (16-18 years) were conducted (Table 1). Guides were developed based on a targeted literature review to investigate preferences for potential features of a combination vaccine. Participants were presented with IMD and vaccines information. Important/least important factors for decision-making were transcribed in response to open-ended/probes questions. FGDs were coded to apply thematic assessment. Results were synthesized separately by moderator-probed and spontaneously mentioned themes. Percentages were calculated on participant numbers contributing to a theme. Results Thirteen participants were included in FGDs (6 Ado, 7 P/C, 57% P/C with college or lower degree, Table 2). Ado preferred a combination vaccine which provided time saving (100%) and convenience (83%) by reducing the number of injections in the immunization series (100%) and number of visits (100%). P/C considered injection site discomfort (71%) as an important decision factor for a combination vaccine, however Ado considered this as least important (100%). Both groups considered impact on healthcare system and environment as least important for a combination vaccine (55%) (Table 3). Cross-protection against other infectious disease (55%, probed) and spontaneous themes (e.g. duration of protection, effectiveness, side effects and dosing interval) emerged (Table 4). These concepts were considered relevant for combination vaccine decision-making, although could be applicable to IMD vaccination more generally. Conclusion The findings suggest vaccine-receivers preferred a combination vaccine covering serogroups A, B, C, W, Y, with simplified schedules (e.g. fewer visits and injections) and potential cross-protection against other infectious diseases. Disclosures Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Linda Hortobagyi, MSc, GSK: Contractor Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Selene Camargo Correa, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds

1136. A Systematic Literature Review of Disparities That May Influence Health Equity in Invasive Meningococcal Disease Prevention in the US

Abstract Background Meningococcal serogroup A, C, W, Y (MenACWY) and B (MenB) vaccines are recommended in the US to prevent invasive meningococcal disease (IMD), a rare but life-threatening disease. Yet the suboptimal uptake of and adherence to these vaccines may relate to inequities for healthcare access. This systematic literature review (SLR) synthesized the US evidence on disparities associated with IMD prevention. Methods Embase, MEDLINE and six conferences were searched and handpicked studies included from 01/01/2012 to 23/08/2022. Studies were screened twice against inclusion criteria (Table 1) via a standardised form. Newcastle Ottawa Scale was used for quality assessment. Synthesis findings reported here were from a broader SLR on IMD risk, prevention and control. Results The SLR found 26 studies, 14 relevant for prevention (Table 2-3). MenACWY series completion had higher odds for adolescents with a family annual income &amp;gt;$75,000 vs. ≤$30,000. Individuals from families below poverty status (annual income ≤$75,000 in 2021) had lower MenB vaccination coverage rates. MenACWY booster compliance was lower in uninsured vs. insured adolescents. Higher odds for ≥1 dose of MenB vaccine were observed if individuals had Medicaid vs. private insurance. For parents/guardians of ≥1 dependent of 16-19 years old, with some insurance was significantly associated with MenB vaccine initiation vs. no insurance. Adolescents living outside a metropolitan statistical area had lower vaccination coverage with ≥1 MenACWY than adolescents in MSA principal cities. MenB series completion rates were lower in rural vs. urban areas in commercial insured populations. Non-Hispanic Black and Hispanic population were more likely to be vaccinated for MenB compared to non-Hispanic Whites, however one study found the opposite. MenB series completion were lower in the Black versus White Medicaid populations. Conclusion Disparities in IMD prevention were reported for race/ethnicity, geographical factors, income/poverty level and health insurance status. Simplification of current recommendation (e.g., combination vaccine with increased convenience and reduced injections in the IMD vaccination schedule) could improve low uptake and adherence in disadvantaged groups. Disclosures Shahina Begum, GSK: Employee Oscar Herrera-Restrepo, PhD, GSK: Stocks/Bonds Catherine Rolland, PhD, Evidera: Advisor/Consultant Sneha Purushotham, MSc, Evidera: Advisor/Consultant Linda Hortobagyi, MSc, GSK: Contractor Zeki Kocaata, PhD, GSK: Stocks/Bonds

1140. Impact of an Implementation Science Initiative to Improve Vaccine Confidence for Invasive Meningococcal Disease (IMD) Prevention within American Indian (AI) Communities

Abstract Background Meningococcal vaccine uptake among adolescents remains suboptimal. This project aimed to identify barriers and motivators for vaccination in AI communities. Methods Between 12/2022 and 2/2023, 3 live family education sessions were held within AI communities in WI and ND. Healthcare provider (HCP) participants also attended a workshop to review current vaccine recommendations. Surveys were administered before/after the workshop and family education sessions. Results Surveys were completed by 56 family members. Baseline confidence in vaccine safety, efficacy and benefit was low, which increased after the sessions (Fig. 1). Parent understanding that the vaccine cannot cause disease improved from 51% to 82% (p =.001). Top reported barriers to vaccination were concern for immediate side effects and long-term side effects, and low perceived risk for IMD (34%, 26%, 25%, respectively). Parents identified learning more about IMD (40%), friends/family getting vaccinated (19%), and a local outbreak (12%) as top motivators to seek vaccination. When asked what they thought would motivate families to seek vaccination, HCPs leading the sessions (n=11) identified learning more about IMD (82%) and friends/family getting vaccinated (27%) only. HCP confidence in counseling families was low and improved after the sessions (Fig. 2). HCPs attending the workshop (n=28) reported discomfort contradicting patients/families as the top challenge in addressing vaccine hesitancy, and more HCPs felt confident having conversations to reduce vaccine hesitancy after the workshop (80%) than before (28%). HCP knowledge improved after the workshop, and more HCPs understood that MenACWY booster doses are not needed when initial vaccination occurs at age ≥16 (50%), and correctly identified “provider recommendation” as the top literature-reported factor influencing parental vaccine decisions (50%) compared to baseline (32% and 14%, respectively). HCP action plans for after the sessions prioritized routinely discussing vaccines at well visits (80%), providing written materials (50%) and staying current on new vaccines (50%). Conclusion Parent and provider knowledge and confidence improved after the program and offered insights into community-level motivators and barriers to vaccination. Disclosures All Authors: No reported disclosures

Acceptance and socioeconomic inequalities in meningococcal B vaccination in the community of Madrid prior to its inclusion in the immunization schedule

IntroductionThe main preventive measure against invasive meningococcal disease is vaccination. The aim of our study was to evaluate the acceptability of the meningococcal B (MenB) vaccine and socioeconomic inequalities in the access to the vaccine in the Community of Madrid in the period prior to its introduction in the immunization schedule. Materials and methodsWe conducted an observational and ecological descriptive study in the cohort of children born between 2016 and 2019 using population-based electronic records. We calculated the vaccination coverage and analysed factors associated with vaccination status, determined the spatial distribution of vaccination coverage and the deprivation index (DI) and assessed the association between them by means of spatial regression. ResultsWe observed an increasing trend in primary vaccination coverage, from 44% in the cohort born in 2016 to 68% in the 2019 cohort. We found a statistically significant association between vaccination status and the DI (OR of primary vaccination in areas with DI5 compared to areas with DP1, 0.38; 95% confidence interval, 0.39−0.50; P<.001). The spatial analysis showed an inverse correlation between the DI and vaccination coverage. ConclusionsThe rise in the coverages of the MenB vaccine shows acceptance by the population. The association between socioeconomic level and vaccination coverage confirms the existence of health inequality and underlines the importance including this vaccine in the immunization schedule.

1150. Invasive meningococcal disease vaccination – a targeted literature review of adolescents and parents/caregivers’ preferences

Abstract Background Invasive meningococcal disease (IMD) serogroups A, B, C, W, Y are commonly prevented by MenACWY and MenB vaccines. MenABCWY candidate vaccines could potentially provide benefits as less injections, simplified schedules, and increased uptake. However, there is limited insight on factors influencing preferences for IMD vaccines/vaccination (Vax). This targeted literature review synthesized evidence of factors influencing IMD Vax preferences in 16–23-year-old adolescents/young adults (Ado/YA) and parents/caregivers (P/CG) of 16-18 year-old adolescents. Methods PubMed and Google Scholar were searched globally to identify publications on IMD Vax attitudes and preferences (Table 1). Studies were restricted to English and published between 2005-2022. Data were extracted and synthesized from full text reviews to list IMD Vax preference attributes. Results From the 77 abstracts screened, 19 publications were extracted (Table 2) and 17 relevant for Ado/YA and P/CG. Knowledge of disease severity (20% of Ado/YA articles) and vaccine (29% of P/CG articles) were the most reported factors influencing Vax preference. Severity of disease increased Vax preference for both groups (14%), while low disease awareness limited P/CGs’ willingness to vaccinate children (14% of P/CG articles). Some Ado/YA preferred fewer injections in the immunization series due to reduced injection site discomforts (13%). P/CG preferred less injections due to less time and less physician visits, as it may reduce vaccine preparation/injection/administration and indirect costs associated with parental work loss (7%). However, their concerns over injection-related pain were a Vax barrier (14%). IMD vaccine effectiveness was recognized by Ado/YA (13%). Longer duration of protection was important for P/CG (14%), whilst herd immunity and direct protection was preferred in Ado/YA (13%). Conclusion Findings highlight IMD Vax characteristics as key considerations among Ado/YA and P/CG when making Vax decisions. To improve vaccination coverage and protection, the evidence supports preferences for vaccinations offering benefits such as fewer injections. Trade-offs between factors relevant for a IMD combination vaccine need further research. Disclosures Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Oscar Herrera-Restrepo, PhD, GSK: Stocks/Bonds Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Willings Botha, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds

Commensal Neisseria cinerea outer membrane vesicles as a platform for the delivery of meningococcal and gonococcal antigens to the immune system

An affordable, accessible, and broadly protective vaccine is required to tackle the re-occurring bacterial meningococcal epidemics in Sub-Saharan Africa as well as an effective control of multi-drug resistant strains of gonococcus. Outer membrane vesicles (OMVs) secreted from Gram-negative bacteria represent an attractive platform for antigen delivery to the immune system and therefore for development of multi-component vaccines. In this study, we describe the generation of modified OMVs (mOMVs) from commensal biosafety-level 1 (BSL-1) Neisseria cinerea ATCC® 14685TM, which is phylogenetically close to the pathogenic bacteria Neisseria meningitidis and Neisseria gonorrhoeae. mOMVs were prepared from N. cinerea engineered to express heterologous antigens from N. meningitidis (factor H binding protein (fHbp) and Neisseria Heparin Binding Antigen (NHBA-2)) and from N. gonorrhoeae (NHBA-542). Mice immunised with the mOMVs produced antibodies against fHbp and NHBA. The work indicates that mOMV from N. cinerea can be used as a platform to induce immune responses against antigens involved in the protective immune response against meningococcal and gonococcal diseases.

Three novel pentavalent meningococcal vaccines.

Invasive meningococcal disease (IMD) is rare in travellers but associated with high mortality and long-term sequelae. Six serogroups (MenABCWXY) account for more than 90% of IMD. Three pentavalent vaccines are on the horizon: two MenABCWY, both with a 0-6months schedule highly immunogenic and well tolerated, and one single-dose MenACWXY.

Distributed genotyping and clustering of Neisseria strains reveal continual emergence of epidemic meningococcus over a century

Core genome multilocus sequence typing (cgMLST) is commonly used to classify bacterial strains into different types, for taxonomical and epidemiological applications. However, cgMLST schemes require central databases for the nomenclature of new alleles and sequence types, which must be synchronized worldwide and involve increasingly intensive calculation and storage demands. Here, we describe a distributed cgMLST (dcgMLST) scheme that does not require a central database of allelic sequences and apply it to study evolutionary patterns of epidemic and endemic strains of the genus Neisseria. We classify 69,994 worldwide Neisseria strains into multi-level clusters that assign species, lineages, and local disease outbreaks. We divide Neisseria meningitidis into 168 endemic lineages and three epidemic lineages responsible for at least 9 epidemics in the past century. According to our analyses, the epidemic and endemic lineages experienced very different population dynamics in the past 100 years. Epidemic lineages repetitively emerged from endemic lineages, disseminated worldwide, and apparently disappeared rapidly afterward. We propose a stepwise model for the evolutionary trajectory of epidemic lineages in Neisseria, and expect that the development of similar dcgMLST schemes will facilitate epidemiological studies of other bacterial pathogens.

Nurse Practitioners’ and Physician Assistants’ Knowledge, Attitudes, and Practices Regarding Meningococcal Vaccination for Healthy Adolescents and Young Adults in the United States

The United States Advisory Committee on Immunization Practices recommends vaccination against meningococcal serogroups A, C, W, and Y for all 11- and 12-year-olds (with a booster dose at age 16) and against meningococcal serogroup B for 16- to 23-year-olds under shared clinical decision making. This study investigated knowledge, attitude, and practices among nurse practitioners and physician assistants regarding meningococcal vaccination. Although nurse practitioners and physician assistants play an important role in discussing and recommending vaccination, knowledge gaps regarding meningococcal disease and vaccination guidelines were identified. Targeted education may promote shared clinical decision making, improving access to meningococcal vaccination.

Characterizing Neisseria meningitidis in Southern Vietnam between 2012 and 2021: A predominance of the chloramphenicol-resistant ST-1576 lineage

ObjectivesOur goal was to describe Invasive Meningococcal Disease (IMD) in Southern Vietnam over the last 10 years. We characterized 109 Neisseria meningitidis strains in Southern Vietnam isolated between 1980s to 2021, that were collected from IMD (n = 44), sexually transmitted infections (n = 2), and healthy carriage (n = 63). MethodsIMD were confirmed by bacterial culture and/or real-time polymerase chain reaction at the national reference laboratory in Pasteur Institute of Ho Chi Minh City (PIHCM). Antimicrobial resistance was determined on 31 IMD and two sexually transmitted infection isolates with E-test for chloramphenicol (CHL), penicillin (PEN), ciprofloxacin (CIP), ceftriaxone (CRO), and rifampicin (RIF). Sequencing was performed for analyzing of multilocus-sequence-typing (MLST), porA, fetA, and antibiotic resistance genes, including gyrA, penA, and rpoB. ResultsThe incidence rate during this period was 0.02 per 100,000 persons/year. Serogroup B accounted for over 90% of cases (50/54). ST-1576 were mainly responsible for IMD, 27/42 MLST profiles, and associated with CHL resistance. Resistance was prevalent among IMD isolates. Thirteen were resistant to CHL (minimum inhibitory concentration [MIC] ≥16 mg/l), 12 were intermediate to PEN (MIC between 0.19 and 0.5 mg/l), and five were CIP-resistant (MIC between 0.19 and 0.5 mg/l). Particularly, one was non-susceptible to CRO (MIC at 0.125 mg/l), belonging to ST-5571 lineage. The resistance was due to carrying resistant alleles of penA and gyrA genes, and catP gene. Notably, seven isolates were resistant/non-susceptible to two or more antibiotics. ConclusionOur results suggest the persistence of the circulating ST-1576 in Southern Vietnam, with a spread of antimicrobial resistance across the community.

EGS P13 Adherence to Guidelines for Post-Splenectomy Patients in a Primary Care Practice in North West England

Abstract Background Splenectomy is indicated in haematological, oncological disorders and occasionally during emergency (trauma) surgery. Given the spleens role in the immunological response, overwhelming infection remains an area of concern for post-splenectomy patients with low prevalence (0.1-0.5%) but high mortality (∼50%). Strep pneumoniae, H influenzae Type B and Neisseria meningitidis are common bacterial perpetrators. At present, Public Health England and the British Society for Haematology recommends regular influenza, pneumococcal and meningococcal vaccinations for patients with asplenia or hyposplenism. They should also be on lifelong prophylactic antibiotics. This audit aimed to assess the adherence to vaccination and antibiotic prophylaxis guidelines for post-splenectomy patients. Methods 19 patients post splenectomy patients were identified at a primary care practice in North West England. Data was retrospectively collected from the last 10 years with two researchers manually searching through their GP records. Parameters collected included both compliance and timeliness with vaccinations and antibiotic prophylaxis as per national guidance. Where there was a deviation from the guidance, the records were again searched to identify any cause. Results 109/162 (67.3%) ‘vaccination opportunities’ for the recommended yearly influenza vaccination were successfully delivered. 17/19 (89.4%) patients had no documented initial pneumococcal vaccination at time of splenectomy. 23/162 (14.2%) influenza and 22/37 (56.4%) pneumococcal vaccination opportunities were missed with no documentation explaining why. Only 1 patient received the recommended MenACWY/MenB vaccination at diagnosis, 5 received delayed vaccinations and 13/19 (68.4%) patients received no meningitis vaccination. 7/19 (37%) patients were not on prophylactic antibiotics as recommended with no documented explanation. 2 of those patients were issued one-off antibiotic prescriptions and 1 had their prescription stopped due to non-compliance. Conclusions Significant improvement is needed with regards to antibiotic prophylaxis, pneumococcal and meningococcal vaccinations with over 50% of vaccinations being missed. Poor documentation and a shift to electronic health records are possible factors that have affected data collection, particularly as a significant number of the splenectomies performed were prior to 2000. Recommendations include routine reviews for asplenic patients, encouragement for opportunistic vaccination and increasing awareness of the risks of post-splenectomy sepsis and the benefits of vaccinations. Future scope could include looking at the same guidelines for other hyposplenic/asplenic conditions.

Epidemic forecast and preparedness for explosive-cerebrospinal meningitis outbreak in Nigeria using the preventive vaccination strategy.

Within the African meningitis belt, yearly outbreaks of cerebrospinal meningitis (CSM), with incidence rates of 10-100 cases per 100 000 population, are typically punctuated by explosive epidemics occurring every 8-12 years, with incidence rates that can exceed 1000 cases per 100 000 population. From 1928 to 2018, Nigeria recorded the highest number (21%) of cases in the region. The reactive vaccination strategy, a protocol with major drawbacks, has been the vaccination method utilised in Nigeria. This review highlights the need for governments within the African meningitis belt to start preparations against the next explosive CSM epidemic expected to occur between 2024 and 2028 using the preventive vaccination strategy. We performed a literature search on the Google Scholar search engine using relevant search strings and included studies and reports between 1905 and 2022 that met set criteria. Neisseria meningitidis serogroups A, B, C, W135, X, and Y; Haemophilus influenzae serotypes a, b, c, e, and f; and Streptococcus pneumoniae serotypes 1, 4, 5, 6, 9, 19, 19F, and 20 were implicated as aetiologies. However, the reactive vaccination strategy was only used against N. meningitidis A or C, H. influenzae b, and pneumococcal conjugate vaccine. Between 2011 and 2017, a polysaccharide vaccine (ACW or ACYW) active against serogroups A, C, W and Y was used within the African meningitis belt for the first time. Varying genotypes of N. meningitidis, H. influenzae and S. pneumoniae were identified. Our results revealed a very high success rate for the preventive vaccination strategy. In order to ensure reductions in the morbidity and mortality associated with invasive CSM, the Federal Ministry of Health, Nigeria, should leverage existing knowledge of the circulating serogroups, serotypes, and genotypes of the primary bacterial aetiologies and commence the implementation of the preventive vaccination strategy.

Molecular characteristics of Neisseria meningitidis carriage strains in university students in Lithuania

BackgroundNeisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of invasive meningococcal disease (IMD). No carriage studies have been performed among the general population in Lithuania, whereas the incidence of IMD in Lithuania was among the highest in European countries from 2009 to 2019.ResultsWe analyzed a total of 401 oropharyngeal samples collected from university students from December 2021 to February 2023 for N. meningitidis carriage using direct swab PCR assays and culture. The overall carriage prevalence based on both or either swab PCR or culture was 4.99%. PCR-based assays were used to characterize 15 carriage isolates, including detection of genogroup, multilocus sequence typing profile, and typing of antigens PorA and FetA. The most common carriage isolates were capsule null locus (cnl), accounting for 46.7%, followed by genogroups B (26.7%) and Y (13.3%). We also performed a molecular characterization of invasive N. meningitidis isolates collected during the COVID-19 pandemic and post-pandemic period to understand better the meningococcal carriage in the context of prevailing invasive strains. Despite the substantial decrease in the incidence of IMD during the 2020–2022 period, clonal complex 32 (CC32) of serogroup B continued to be the most prevalent IMD-causing CC in Lithuania. However, CC32 was not detected among carriage isolates. The most common CCs were CC269, CC198, and CC1136. The antigen peptide variants found in most carried isolates were classified as ‘insufficient data’ according to the MenDeVAR Index to evaluate the potential coverage by the 4CMenB vaccine. Nearly half of the isolates were potentially covered by the Men-Fhbp vaccine. Resistance to ciprofloxacin was detected only for one cnl isolate. All isolates were susceptible to penicillin and ceftriaxone. Our analysis identified frequent partying (≥ 4 times/month) as a risk factor for meningococcal carriage, whereas smoking, living in a dormitory, and previous COVID-19 illness were not associated with the carriage.ConclusionsOur study revealed a low prevalence of meningococcal carriage among university students in Lithuania. The carriage isolates showed genetic diversity, although almost half of them were identified as having a null capsule locus.

Meningococcal Surveillance Australia - Reporting period 1 January to 31 March 2023.

The reference laboratories of the National Neisseria Network, Australia report data on invasive meningococcal disease (IMD) cases confirmed by culture and/or molecular techniques for the Australian Meningococcal Surveillance Programme (AMSP). Culture-positive cases and molecular-based diagnoses are defined as IMD by the Communicable Diseases Network Australia National Guidelines for Public Health Units.1 Data contained in the quarterly reports are restricted to a description of the number of cases by jurisdiction and serogroup, when known. Some minor corrections to data in Table 1 may be made in subsequent reports if additional data are received. IMD notifications in Australia in the first quarter of 2023 were greater than in the corresponding period in 2022 but still below the 36 IMD cases reported in quarter one of 2019 (prior to the SARS-CoV-2 pandemic).2 Notably, the predominance of N. meningitidis serogroup B (MenB) IMD continued in the first quarter of 2023 (21/23, 91.3% of notifications), showing an increase from 84% in the fourth quarter of 2022.3 In contrast, between 2019 and 2021, 50–62% of IMD was attributable to MenB.4 A full analysis of laboratory-confirmed cases of IMD in each calendar year is contained in the AMSP annual report published in Communicable Diseases Intelligence.

Epidemiology of Invasive Meningococcal Disease in Colombia: A Retrospective Surveillance Database Analysis.

Invasive meningococcal disease (IMD), caused by Neisseria meningitidis, is associated with high morbidity and mortality. The aim of the current study was to describe the historical and recent epidemiology of IMD in Colombia. This retrospective surveillance database analysis examined all available data on IMD in Colombia. Data were extracted from publicly available disease event reports and laboratory surveillance reports or obtained directly from hospitals in Cartagena. During 2015-2021, the overall incidence of IMD was 0.04-0.18 per 100,000 based on laboratory surveillance reports. IMD incidence was highest among infants aged<1year (0.52-1.47 per 100,000), as was IMD mortality (0.00-0.65 per 100,000). Serogroup B was the dominant serogroup responsible for IMD in Colombia during 1988-2014, but, since 2015, serogroup C has been dominant in all age groups, followed by serogroups B and Y. During 2010-2021 combined, the majority of IMD cases were reported in Bogotá (31.9%) and Antioquia (21.7%). Of 42 IMD cases in the city of Cartagena, 54.8% occurred in people who lived in the poorest neighborhoods, and these patients had the highest IMD lethality (52.2%) and the shortest median hospitalization duration (3days). The overall incidence of IMD in Colombia was low but was highest among infants aged<1year. IMD cases tended to be concentrated in the more densely populated areas and in poorer neighborhoods. As the majority of IMD cases in Colombia since 2015 have been serogroup C, followed by B or Y, vaccination to protect against these serogroups could potentially be beneficial and help to achieve the World Health Organization's and Pan American Health Organization's roadmaps to defeat meningitis by 2030.

Mechanism of substrate binding and transport in BASS transporters

The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBTNM) in complex with pantoate, a potential substrate of ASBTNM. The BASS family is characterised by two helices that cross-over in the centre of the protein in an arrangement that is intricately held together by two sodium ions. We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. During molecular dynamics simulations the pantoate remains in this position when sodium ions are present but is more mobile in their absence. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBTNM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.

Mechanism of substrate binding and transport in BASS transporters.

The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBTNM) in complex with pantoate, a potential substrate of ASBTNM. The BASS family is characterised by two helices that cross-over in the centre of the protein in an arrangement that is intricately held together by two sodium ions. We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. During molecular dynamics simulations the pantoate remains in this position when sodium ions are present but is more mobile in their absence. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBTNM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.