Invasive Meningococcal Disease Research Articles

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 >$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

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

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.

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.

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.

Informing the use of a supplementary immunisation programme for the management of a community cluster of invasive meningococcal disease, Yorkshire, 2022

ObjectivesTo outline the management of a community cluster of serogroup B invasive meningococcal disease (IMD) cases, including key factors for decision making and the choice and implementation of control measures. Study designDescriptive report of cluster management. MethodsSubtyping of IMD cases identified a number of potentially linked cases in a defined geographical area. An Incident Management Team (IMT) was convened to coordinate the public health response. A case definition was developed in order to identify further cases within the cluster. ResultsFour cases of IMD met the case definition and were initially considered as part of this cluster. Three resided in the same small town, which was the focus for public health management. The IMT agreed that it would be proportionate to instigate additional control measures. The population at higher risk of infection were identified, and a supplementary vaccination programme was rolled out in the community. Over five clinics, 45.6% (639/1401) of the target cohort received at least one dose of the vaccine, with 34.7% (486/1401) receiving both doses. Inequalities in uptake were observed by sex, age and deprivation. ConclusionsDecision making for public health responses to IMD clusters is complex. Informed by epidemiological evidence, numerous partners engaged in collaborative decision making, which was critical for the effective implementation of the community response. Links between the local authority public health team and the community enabled the use of existing structures and relationships to maximise the number of vaccinations delivered. No further cases of IMD linked to this cluster were identified.

Detection of Novel US Neisseria meningitidis Urethritis Clade Subtypes in Japan.

Neisseria meningitidis causes invasive meningococcal diseases and has also been identified as a causative agent of sexually transmitted infections, including urethritis. Unencapsulated sequence type 11 meningococci containing the gonococcal aniA-norB locus and belonging to the United States N. meningitidis urethritis clade (US_NmUC) are causative agents of urethral infections in the United States, predominantly among men who have sex with men. We identified 2 subtypes of unencapsulated sequence type 11 meningococci in Japan that were phylogenetically close to US_NmUC, designated as the Japan N. meningitidis urethritis clade (J_NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US_NmUC and J_NmUS urethritis-associated meningococci is disseminated worldwide. Global monitoring of urethritis-associated N. meningitidis isolates should be performed to further characterize microbiologic and epidemiologic characteristics of urethritis clade meningococci.

Inference of transmission dynamics and retrospective forecast of invasive meningococcal disease.

The pathogenic bacteria Neisseria meningitidis, which causes invasive meningococcal disease (IMD), predominantly colonizes humans asymptomatically; however, invasive disease occurs in a small proportion of the population. Here, we explore the seasonality of IMD and develop and validate a suite of models for simulating and forecasting disease outcomes in the United States. We combine the models into multi-model ensembles (MME) based on the past performance of the individual models, as well as a naive equally weighted aggregation, and compare the retrospective forecast performance over a six-month forecast horizon. Deployment of the complete vaccination regimen, introduced in 2011, coincided with a change in the periodicity of IMD, suggesting altered transmission dynamics. We found that a model forced with the period obtained by local power wavelet decomposition best fit and forecast observations. In addition, the MME performed the best across the entire study period. Finally, our study included US-level data until 2022, allowing study of a possible IMD rebound after relaxation of non-pharmaceutical interventions imposed in response to the COVID-19 pandemic; however, no evidence of a rebound was found. Our findings demonstrate the ability of process-based models to retrospectively forecast IMD and provide a first analysis of the seasonality of IMD before and after the complete vaccination regimen.

Aceptación y desigualdades socioeconómicas en la vacunación frente a meningococo B en la Comunidad de Madrid en el periodo anterior a su inclusión en el calendario

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.

The rapid rebound of invasive meningococcal disease in France at the end of 2022

BackgroundInvasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical measures to control the COVID-19 pandemic. A rebound in IMD cases was feared upon easing these measures. MethodsWe conducted a retrospective descriptive study using the French National Reference Center Database for meningococci between 2015 and 2022. We scored serogroups, sex, age groups, and clonal complexes of the corresponding isolates. FindingsOur data clearly show a decline in the number of IMD cases for all serogroups and age groups until 2021. This decline was mainly due to a decrease in IMD cases provoked by the hyperinvasive ST-11 clonal complex. However, since the fall of 2021, there has been an increase in IMD cases, which accelerated in the second half of 2022. This rebound concerned all age groups, in particular 16–24 years. The increase in cases due to serogroups B, W, and Y were mainly due to the expansion of isolates of the ST-7460, the clonal complex ST-9316 and the clonal complex ST-23, respectively. InterpretationIMD epidemiology changes constantly and profound epidemiological changes have been recently observed. The surveillance of IMD needs to be enhanced using molecular tools. Additionally, vaccination strategies need to be updated to acknowledge recent epidemiological changes of these vaccine-preventable serogroups.

Range of Clinical Manifestations Caused by Invasive Meningococcal Disease Due to Serogroup W: A Systematic Review.

Invasive meningococcal disease (IMD) due to serogroup W meningococci (MenW) is consistently reported with atypical clinical manifestations, including gastrointestinal symptoms, bacteremic pneumonia, and septic arthritis. We undertook a systematic review of the literature for a comprehensive assessment of the clinical presentation of IMD caused by MenW. PubMed and Embase databases were searched from inception to June 2022 using a combination of MeSH terms and free text for articles that reported symptoms and signs of MenW IMD, and associated manifestations. The most commonly reported symptoms identified included: fever (range 36-100% of cases), nausea and/or vomiting (range 38-47%), vomiting (range 14-68%), cough (range 7-57%), sore throat (range 13-34%), headache (range 7-50%), diarrhea (range 8-47%), altered consciousness/mental status (range 7-38%), stiff neck (range 7-54%), and nausea (range 7-20%). Sepsis (range 15-83% of cases) was the most commonly reported manifestation followed by meningitis (range 5-72%), sepsis and meningitis (range 6-74%), bacteremic pneumonia (range 4-24%), arthritis (range 1-15%), and other manifestations (e.g., pharyngitis/epiglottitis/supraglottitis/tonsillitis/conjunctivitis; range 1-24%). The case fatality rates ranged from 8-40%, and among the survivors 4-14% had long-term sequelae. Clinicians need to be aware of the nonspecific symptoms and signs of IMD, as well as of the atypical manifestations in regions where MenW is known to circulate to ensure timely diagnoses and treatment.

Epidemiological and strain characteristics of invasive meningococcal disease prior to, during and after COVID-19 pandemic restrictions in England

In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal disease in the three years prior to the COVID-19 pandemic, and the three years immediately after the introduction of restrictions. The UK Health Security Agency conducts national meningococcal disease surveillance in England consisting of laboratory-based case confirmation with strain characterisation by culture and/or molecular detection, as well as clinical follow-up of all cases. In the pre-pandemic period, 554-742 IMD cases were laboratory-confirmed per year. MenB caused 57.2% of cases, followed by MenW (22.7%), MenY (10.6%) and MenC (7.7%). The introduction of restrictions in late March 2020 led to a 73% reduction in IMD. After the removal of restrictions in 2021, a resurgence in MenB was observed, primarily in teenagers and young adults. During the following winter period (2022/23), MenB disease increased to the highest level since 2012 with cases rising across multiple age groups, however, cases in young children eligible for MenB vaccination remained lower than prior to the pandemic. MenACWY cases remained very low throughout the pandemic period. Once pandemic restrictions in England were removed, MenB quickly rebounded- initially driven by a resurgence in teenagers/young adults, but later among other age groups. MenACWY cases remain very low due to the protection afforded by the adolescent MenACWY conjugate vaccine programme.

A National Advisory Committee on Immunization (NACI) update on invasive meningococcal disease (IMD) epidemiology and program-relevant considerations for preventing IMD in individuals at high risk of exposure.

Following recent outbreaks of invasive meningococcal disease (IMD) in Canada and updates to provincial vaccination guidelines, the National Advisory Committee on Immunization (NACI) conducted a targeted review of evidence with a focus on immunization of adolescents and young adults. NACI reviewed national and international immunization recommendations for populations at high-risk of IMD, national IMD epidemiology and program-relevant considerations. Given the varied IMD epidemiology, NACI determined that recommending a pan-Canadian targeted program is currently challenging and that regional programs may be better suited to prevent IMD in population groups considered to be at high-risk of exposure. Further data is needed to ascertain contemporary risk factors for IMD (including activities and settings associated with bacterial acquisition, carriage and transmission) and estimate the true cost of meningococcal vaccine-preventable infections in Canada. To support provinces and territories in their decision-making, an outline of program-relevant elements for provincial and territorial consideration is provided.

Invasive Disease Due to Neisseria meningitidis: Surveillance and Trends in Israel Prior to and during the COVID-19 Pandemic.

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study's aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998-2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020-2022 vs. 0.9/100,000 in 1998-2019). The number of notified IMD cases declined by 65% in 2020-2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007-2022). Mortality risk markers included cases' age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0-9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs.

Accuracy of antigen tests for meningococcal meningitis in cerebrospinal fluid: A diagnostic meta-analysis.

Neisseria meningitidis is one of the major pathogens of meningitis in children worldwide and causes invasive meningococcal disease (IMD), which is a critical illness that mainly presents as meningitis and/or septicemia in children. Identification of N. meningitidis in cerebrospinal fluid (CSF) is the gold standard for the diagnosis of meningococcal meningitis, but antigen tests have advantages such as timely results, relatively low cost, and convenience. Yet, the diagnostic accuracy of antigen tests remains uncertain. Therefore, the aim of this meta-analysis was to evaluate the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We searched the PubMed, Embase, and Cochrane Library databases for studies evaluating the diagnostic accuracy of antigen tests for N. meningitidis in CSF. We included studies that provided sufficient data to construct a 2 × 2 table on a per-sample basis. To determine the overall sensitivity and specificity of the antigen tests, we used polymerase chain reaction (PCR) as the reference standard and employed the hierarchical summary receiver operating characteristic model. Nine studies with 4533 CSF samples were included. The meta-analysis yielded a pooled sensitivity of 91.2% (95% confidence interval [CI]: 80.0%-100.0%) and a pooled specificity of 93.8% (95% CI: 83.9%-100.0%). A subgroup analysis of 2 studies that reported the outcomes of MeningoSpeed yielded a pooled sensitivity of 93.4% (95% CI: 90.0%-95.8%) and a pooled specificity of 91.9% (95% CI: 88.6%-94.4%). Antigen testing for the N. meningitidis serogroup X had a pooled sensitivity of 92.4% (95% CI: 85.2%-96.2%) and a pooled specificity of 99.2% (95% CI: 78.7%-100.0%). The studied antigen tests had high sensitivity and specificity for the diagnosis of meningococcal meningitis in CSF specimens. Antigen testing could serve as an accurate diagnostic method for assessing patients who have a suspected N. meningitidis infection.

Antibodies against Neisseria meningitidis serogroups A, C, W and Y in serum and saliva of Norwegian adolescents

IntroductionThe incidence of invasive meningococcal disease (IMD) among Norwegian 16–19-year-olds was 1–7/100,000 in the decade before the COVID-19 pandemic, with serogroup Y (MenY) dominance. In contrast to many other European countries, meningococcal vaccines are not part of the national immunisation program (NIP) in Norway. This cross-sectional study aimed to measure the degree of natural immunity against Neisseria meningitidis among adolescents in Norway to evaluate the need for introducing tetravalent meningococcal conjugate vaccine (MCV4) in the NIP. Materials and methodsSerum and saliva samples were collected from students in upper and lower secondary schools in Norway in 2018. Samples were analysed for meningococcal capsular polysaccharide (PS)-specific antibodies using a bead-based multiplex immunoassay. PS-specific antibody levels were linked to data on meningococcal carriage, vaccination status and risk factors for carriage (assessed with questionnaire) and analysed by linear regression of log transformed concentrations. A subset of samples from unvaccinated individuals was analysed for serum bactericidal antibodies (SBA). ResultsA total of 1344 participants, median age 16 years (range 12–24), were included in the study. Overall, 60.9% of the participants were female and 1137 (84.6%) were not vaccinated with MCV4. PS-specific antibody concentrations in serum and saliva were low among unvaccinated individuals for all serogroups and only 6.7–20.0% of the subpopulation with high PS-specific antibodies assessed with SBA had protective levels. Unvaccinated MenY carriers had higher levels of MenY anti-PS IgG in serum and IgA in saliva than those not carrying MenY. Use of Swedish snus was associated with lower anti-PS IgG levels in serum and waterpipe use with lower anti-PS IgG levels in saliva. ConclusionUnvaccinated adolescents in Norway have a low degree of natural immunity against the serogroups of N. meningitidis predominating among cases of IMD in this age group. Therefore, introduction of MCV4 for adolescents in the NIP is recommended.

Australian Meningococcal Surveillance Programme Annual Report, 2022.

In Australia, both probable and laboratory-confirmed cases of invasive meningococcal disease (IMD) are reported to the National Notifiable Diseases Surveillance System (NNDSS). Compared to 2021, the number of IMD notifications in 2022 increased by 81% to 127, alongside the easing of COVID-19 containment measures. Laboratory confirmation occurred in 95% of these cases, with 51% (62/121) diagnosed by bacterial culture and 49% (59/121) by nucleic acid amplification testing. The serogroup was determined for 97% of laboratory-confirmed cases (117/121): serogroup B (MenB) accounted for 83% of infections (100/121); MenW for 4% (5/121); MenY for 10% (12/121); no infections were attributed to MenC disease. Fine typing was available on 67% of the cases for which the serogroup was determined (78/117). In MenB isolates, 27 porA types were detected, the most prevalent of which were P1.7-2,4 (18%;11/62), P1.22,14 (15%; 9/62), P1.18-1,34 (10%; 6/62) and P1.7,16-26 (10%; 6/62). All five MenW infections identified as porA type P1.5,2 with different MLST sequence types (ST): 11, 574, 1287, 12351, 13135 all belonging to clonal complex 11, the hypervirulent strain reported in outbreaks in Australia and overseas. In MenY, the predominant porA type was P1.5-1,10-1 (73%; 8/11), ST 1655 and from clonal complex 23. Children less than 5 years of age and people aged 15-19 years were overrepresented with IMD notifications, accounting for 22% (27/121) and 23% (28/121) of laboratory-confirmed cases respectively. Fifteen percent of laboratory-confirmed notifications (18/121) were in persons aged 45-64 years. MenB infections were detected in all age groups but predominated in persons aged 15-19 years (93% of IMD in this age group; 26/28) and comprised 89% (24/27) of infections in children aged less than 5 years. MenW infections were markedly reduced in 2022, accounting for two IMD detections in children 1-4 years (2/16) and sporadic detections in other older age groups. MenY infections were largely detected in adults aged 45-64 years, accounting for 28% of IMD in this age group (5/18). All 62 cultured IMD isolates had antimicrobial susceptibility testing performed. Minimum inhibitory concentration (MIC) values were categorised using Clinical Laboratory Standards Institute (CLSI) interpretative criteria: 5% (3/62) were defined as penicillin resistant (MIC value ≥ 0.5 mg/L); 71% (44/62) had intermediate susceptibility to penicillin (MIC values 0.125 and 0.25 mg/L) and 24% (15/62) were susceptible to penicillin. All isolates were susceptible to ceftriaxone, ciprofloxacin and rifampicin.

Four-Component Recombinant Protein–Based Vaccine Effectiveness Against Serogroup B Meningococcal Disease in Italy

Population-based data on the 4-component recombinant protein-based (4CMenB) vaccine effectiveness and reduction in incidence rate ratios (IRRs) are continuously needed to assess vaccine performance in the prevention of serogroup B invasive meningococcal disease (IMD). To assess the effectiveness and reduction in IRRs associated with the 4CMenB vaccine in the pediatric population in 6 regions in Italy. This retrospective cohort screening study and case-control study included data from children aged younger than 6 years in 6 highly populated Italian regions from January 1, 2006, to January 1, 2020. Participants included children younger than 6 years diagnosed with serogroup B IMD without predisposing factors. Data were collected from regional surveillance and vaccination registries and were analyzed from September 2021 to January 2022. Routine 4CMenB vaccination, per regional vaccination programs. The main outcome was the effectiveness of the 4CMenB vaccine in the prevention of serogroup B IMD in the population of children aged younger than 6 years in 6 Italian regions. The percentages of vaccine effectiveness (VE) were obtained through the concomitant use of a screening method and a case-control study. Secondary outcomes were the comparison of effectiveness results obtained using the 2 different computational methods, the description of serogroup B IMD incidence rates, and reduction in IRRs before and after 4CMenB introduction, as a proxy for vaccine impact. The cohort screening study included a resident population of 587 561 children younger than 6 years in 3 regions with similar surveillance protocols, and the matched-case controls study assessed a resident population of 1 080 620 children younger than 6 years in 6 regions. Analyses found that 4CMenB VE in fully immunized children was 94.9% (95% CI, 83.1%-98.4%) using the screening method and 91.7% (95% CI, 24.4%-98.6%) using the case-control method. Overall reduction in IRR was 50%, reaching 70% in regions with early-start vaccination schedules. The case-control method involving 6 highly-populated Italian regions included 26 cases and 52 controls and found an estimated VE of 92.4% (95% CI, 67.6%-97.9%) in children old enough for the first vaccine dose and 95.6% (95% CI, 71.7%-99.1%) in fully immunized children. VE was more than 90% for partially immunized children. Even in regions where the first dose was administered at age 2 months, almost 20% of unvaccinated cases were among infants too young to receive the first 4CMenB dose. This screening cohort study and matched case-controls study found high effectiveness of 4CMenB vaccination and greater reduction in IRR for early-start vaccination schedules in preventing invasive serogroup B meningococcal disease. The high proportion of children too young to be vaccinated among unvaccinated cases suggests that starting the vaccination even earlier may prevent more cases. Screening and case-control methods provided similar estimates of VE: either method may be used in different study settings, but concomitant use can provide more robust estimates.