Neisseria Meningitidis Serogroup Research Articles

Statewide Outbreak of Neisseria meningitidis Serogroup Y, Sequence Type 1466 - Virginia, 2022-2024.

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

Characterisation and Immunogenicity of Neisseria cinerea outer membrane vesicles displaying NadA, NHBA and fHbp from Neisseria meningitidis serogroup B.

More affordable and effective vaccines against bacterial meningitis caused by Neisseria meningitidis serogroup B are still required for global prevention. We have previously shown that modified outer membrane vesicles (mOMVs) from commensal Neisseria cinerea can be used as a platform to induce immune responses against meningococcal antigens. The aim of the present study was to use a combination of two genetically engineered mOMVs to express multiple antigens from N. meningitidis known to be involved in protective immunity to meningococcal meningitis (different variants of factor H binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisseria Adhesin A (NadA)). Antigen expression in the mOMVs was confirmed by Western blotting; detoxification of the lipooligosaccharide (LOS) was confirmed by measuring human Toll-like receptor 4 (hTLR4) activation using in vitro cell assays. Mice immunised with a combination of two mOMVs expressing fHbp, NHBA and NadA produced antibodies to all the antigens. Furthermore, serum bactericidal activity (SBA) was induced by the immunisation, with mOMVs expressing NadA displaying high SBA titres against a nadA+ MenB strain. The work highlights the potential of mOMVs from N. cinerea to induce functional immune responses against multiple antigens involved in the protective immune response to meningococcal disease.

Economic evaluation on meningococcal vaccination strategies among children under nine years of age in Zhejiang province, China.

Meningococcal vaccination in Chinese national immunization program (NIP) includes polysaccharide vaccine against Neisseria meningitidis serogroup A (MPV-A) and polysaccharide vaccine against Neisseria meningitidis serogroup A and C(MPV-AC). This study aimed to assess the cost-effectiveness of an alternative strategy using polysaccharide conjugate vaccine against Neisseria meningitidis serogroup A,C,W,Y(MCV-ACWY) and polysaccharide vaccine against Neisseria meningitidis serogroup A,C,W,Y(MPV-ACWY). From a societal perspective, we constructed a decision tree-Markov model to simulate the economic and health consequences of meningococcal disease in a 2023 birth cohort with the current meningococcal vaccination strategy and the alternative. Parameters of epidemiology, vaccine efficacy, cost, and utility were extracted from database and previous literatures. The sensitivity analysis was implemented to evaluate the robustness of the model. Compared to the current practice, the alternative strategy could avoid 513 meningococcal disease cases, 53 sequelae and 47 deaths. The ICER was estimated at $16899.81 /QALY, under the threshold of one time of the GDP per capita of Zhejiang province in 2023. The incidence of meningococcemia, the incidence of meningococcal meningitis, the case fatality of meningococcemia, the vaccine efficacy of MCV-ACWY and the price of MCV-ACWY would influence the cost-effectiveness of the meningococcal vaccination strategies. At the threshold, the probability of cost-effectiveness was 14.76% for the current strategy and 55.98% for the alternative strategy, respectively. The current meningococcal vaccination strategy had effectively prevented meningococcal disease at a low cost, but with limited serogroup coverage. Strategy using MCV-ACWY and MPV-ACWY could increase health benefits at a substantial cost at a cost-effective manner.

Risk factors associated with meningitis outbreak in the Upper West Region of Ghana: A matched case-control study.

The Northern part of Ghana lies within the African meningitis belt and has historically been experiencing seasonal meningitis outbreaks. Despite the continuous meningitis outbreak in the region, the risk factors contributing to the occurrence of these outbreaks have not been clearly identified. This study, therefore, sought to describe the clinical characteristics and possible risk factors associated with meningitis outbreaks in the Upper West Region (UWR). A 1:2 matched case-control study was conducted in May-December 2021 to retrospectively investigate possible risk factors for meningitis outbreak in the UWR of Ghana between January and December 2020. Cases were persons with laboratory confirmed meningitis, and controls were persons of similar age and sex without meningitis living in the same house or neighborhood with a confirmed case. Both primary and secondary data including clinical, socio-demographic and laboratory information were collected and entered on standard questionnaires. Data was analyzed using descriptive statistics and conditional logistic regression. Meningitis cases were mostly due to Streptococcus pneumoniae (67/98; 68.37%), followed by Neisseria meningitides serogroup X (27/98; 27.55%). Fever occurred in 94.03% (63/67) of Streptococcus pneumoniae cases and 100% in both Neisseria meningitidis serogroup X (27/27) and Neisseria meningitidis serogroup W groups (3/3). CSF white cell count was significantly associated with the causative agents of meningitis. Conditional logistic regression analysis showed that, passive exposure to tobacco [AOR = 3.65, 95%CI = 1.03-12.96], bedrooms with 3 or more people [AOR = 4.70, 95%CI = 1.48-14.89] and persons with sore throat infection [AOR = 8.97, 95%CI = 2.73-29.43] were independent risk factors for meningitis infection. Headache, fever and neck pain continue to be the most common symptoms reported by meningitis patients. Education and other preventive interventions targeting exposure to tobacco smoke and crowded rooms would be helpful in reducing meningitis outbreaks in the Upper West Region of Ghana.

Neisserial adhesin A (NadA) binds human Siglec-5 and Siglec-14 with high affinity and promotes bacterial adhesion/invasion.

Neisserial adhesin A (NadA) is a meningococcal surface protein included as recombinant antigen in 4CMenB, a protein-based vaccine able to induce protective immune responses against Neisseria meningitidis serogroup B (MenB). Although NadA is involved in the adhesion/invasion of epithelial cells and human myeloid cells, its function in meningococcal physiology is still poorly understood. To clarify the role played by NadA in the host-pathogen interaction, we sought to identify its cellular receptors. We screened a protein microarray encompassing 2,846 human and 297 mouse surface/secreted recombinant proteins using recombinant NadA as probe. Efficient NadA binding was revealed on the paired sialic acid-binding immunoglobulin-type lectins receptors 5 and 14 (Siglec-5 and Siglec-14), but not on Siglec-9 therein used as control. The interaction was confirmed by biochemical tools with the determination of the KD value in the order of nanomolar and the identification of the NadA binding site by hydrogen-deuterium exchange coupled to mass spectrometry. The N-terminal domain of the Siglec-5 that recognizes the sialic acid was identified as the NadA binding domain. Intriguingly, exogenously added recombinant soluble Siglecs, including Siglec-9, were found to decorate N. meningitidis surface in a NadA-dependent manner. However, Siglec-5 and Siglec-14 transiently expressed in CHO-K1 cells endorsed NadA binding and increased N. meningitidis adhesion/invasion while Siglec-9 did not. Taken together, Siglec-5 and Siglec-14 satisfy all features of NadA receptors suggesting a possible role of NadA in the acute meningococcal infection.IMPORTANCEBacteria have developed several strategies for cell colonization and immune evasion. Knowledge of the host and pathogen factors involved in these mechanisms is crucial to build efficacious countermoves. Neisserial adhesin A (NadA) is a meningococcal surface protein included in the anti-meningococcus B vaccine 4CMenB, which mediates adhesion to and invasion of epithelial cells. Although NadA has been shown to bind to other cell types, like myeloid and endothelial cells, it still remains orphan of a defined host receptor. We have identified two strong NadA interactors, Siglec-5 and Siglec-14, which are mainly expressed on myeloid cells. This showcases that NadA is an additional and key player among the Neisseria meningitidis factors targeting immune cells. We thus provide novel insights on the strategies exploited by N. meningitidis during the infection process, which can progress to a severe illness and death.

Effectiveness of MenB-4C vaccine against gonorrhea: a systematic review and meta-analysis.

There is no licensed vaccine against gonorrhea but Neisseria meningitidis serogroup B outer membrane vesicle-based vaccines, like MenB-4C, may offer cross-protection against gonorrhea. This systematic review and meta-analysis synthesized the published literature on MenB-4C vaccine effectiveness against gonorrhea. We conducted a literature search of electronic databases (PubMed, Medline, Embase, Global Health, Scopus, Google Scholar, CINAHL, and Cochrane Library) to identify peer-reviewed papers, published in English, from 1/1/2013-7/12/2024 that reported MenB-4C vaccine effectiveness estimates against gonorrhea and gonorrhea/chlamydia co-infection, and the duration of MenB-4C vaccine-induced protection. We estimated pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea using the DerSimonian-Laird random effects model. Eight papers met our eligibility criteria. Receipt of ≥1 dose of MenB-4C vaccine was 23%-47% effective against gonorrhea. Two doses of MenB-4C vaccine were 33-40% effective against gonorrhea and one dose of MenB-4C vaccine was 26% effective. MenB-4C vaccine effectiveness against gonorrhea/chlamydia co-infection was mixed with two studies reporting effectiveness estimates of 32% and 44%, and two other studies showing no protective effect. MenB-4C vaccine effectiveness against gonorrhea was comparable in people living with HIV (44%) and people not living with HIV (23%-47%). Pooled MenB-4C vaccine effectiveness (≥1 dose) against gonorrhea was 32.4%. One study concluded that MenB-4C vaccine effectiveness against gonorrhea may wane approximately 36 months post-vaccination. MenB-4C vaccine is moderately effective against gonorrhea in various populations. Prospective clinical trials that assess the efficacy of MenB-4C against gonorrhea, gonorrhea/chlamydia co-infection, and duration of protection are warranted to strengthen this evidence.

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

ABSTRACT 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.

An Investigation of Ciprofloxacin-resistant Neisseria Meningitidis Serogroup B Infection Outbreak in a Provincial Prison, Nan Province, Thailand, October 2023

Meningococcal infection is a severe illness that can result in organ damage or death. On 23 Oct 2023, a joint investigation team was notified about two inmates diagnosed with meningococcal infection in a provincial prison. The investigation aimed to confirm the outbreak, describe epidemiological characteristics, determine possible source and risks of infection, and provide recommendations and control measures. This study reviewed the situation using surveillance databases. Active case finding was conducted among inmates and prison staff. Close contacts were identified and assessed. Drug sensitivity and serogroup identification were done in the cultured-growth specimens. Surveying inmate rooms, observing inmates' behaviors, and interviewing inmates and prison staff were performed. There were 7 laboratory-confirmed cases identified (attack rate 0.5%). All cases were male inmates with a median age of 46 years (interquartile range 38.5–49.5 years). Common symptoms were fever (100%) and headache (71%). Eight cases required hospital admission and one dead case was found (CFR 14%). Among 609 close contacts, 99% were inmates. All cultured-growth specimens were Neisseria meningitidis serogroup B with ciprofloxacin resistance. Crowded inmates and sharing water cups were risk factors for intra-room spreading. Daily activities and the previous influenza outbreak promoted inmates' inter-room contact. This is the ciprofloxacin-resistant serogroup B meningococcal disease outbreak in a provincial prison revealing multiple factors, including environmental, behaviors and daily activities, that promoted the disease's spread. Rifampicin chemoprophylaxis, active surveillance, and limited inmate activities could help reduce disease spread.

Bactericidal human monoclonal antibody 1B1 shows specificity for meningococcal factor H binding protein variant 2 and displaces human factor H.

Thousands of disease cases and hundreds of deaths occur globally each year due to invasive meningococcal disease. Neisseria meningitidis serogroup B (MenB) is the leading cause of such disease in developed countries. Two vaccines, 4CMenB and MenB-fHbp, that protect against MenB are available and include one or two forms respectively of factor H binding protein (fHbp), a key protective antigen. Studies of circulating meningococci have identified over 1380 different fHbp amino acid sequences, which form three immunologically distinct clusters, termed variants 1, 2, and 3. Neither of the current vaccines contains a variant 2 antigen, which is less well characterized than fHbp variants 1 and 3. We characterized the interaction of fHbp variant 2 with humAb 1B1 using biochemical methods and live meningococcal assays. Further, we determined the crystal structure of the complex at 2.4 Å resolution, clearly revealing the epitope and providing the first detailed report of an antibody with distinct specificity for fHbp variant 2. Extensive mutagenesis and binding studies elucidated key hotspots in the interface. This combination of structural and functional studies provides a molecular explanation for the bactericidal potency and specificity of humAb 1B1 for fHbp variant 2. Our studies, focused on fHbp variant 2, expand the understanding of this previously under characterized group of the vast family of variants of fHbp, a virulence factor present on all meningococci. Moreover, the definition of a protective conformational epitope on fHbp variant 2 may support the design and development of novel variant 2-containing MenB vaccines affording greater breadth of protection.

A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C.

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice. The individual levels of antibodies formed were compared and classified as highly glycan-specific and protective. All glycoconjugates induced a stable and long-term IgG response and binding to the native CPS epitope was achieved. The generated antibodies were protective against MenC and/or MenB; this was validated in vitro by SBA and OPKA assays. By merging the fluorinated glycan epitope of MenC with an outer cell membrane protein of MenB, a bivalent vaccine against both serogroups was created. It is envisaged that validation of this synthetic, fluorinated disialoside bioisostere as a potent antigen will open new therapeutic avenues.

Concurrent Outbreaks of Hepatitis A, Invasive Meningococcal Disease, and Mpox, Florida, USA, 2021-2022.

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Penbraya: A pentavalent meningococcal vaccine.

The FDA has licensed Penbraya (Pfizer), a pentavalent polysaccharide conjugate meningococcal vaccine, for prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, B, C, W, or Y (MenABCWY) in persons 10-25 years old. Penbraya is the only meningococcal vaccine that contains all five of these serogroups. Two quadrivalent polysaccharide conjugate meningococcal vaccines containing serogroups A, C, W, and Y (MenACWY; Menveo, MenQuadfi) and two meningococcal serogroup B vaccines (MenB; Bexsero, Trumenba) are available in the US.

Cost of Illness Analysis of Invasive Meningococcal Disease Caused by Neisseria Meningitidis Serogroup B in the Netherlands-a Holistic Approach.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a rapidly progressing, rare disease that often presents as meningitis or sepsis. It mostly affects infants and adolescents, with high fatality rates or long-term sequelae. In the Netherlands, serogroup B (MenB) is most prevalent. We aimed to estimate the economic burden of MenB-related IMD between 2015 and 2019, including direct and indirect medical costs from short- and long-term sequelae, from a societal perspective. IMD incidence was based on laboratory-based case numbers from the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam UMC, Amsterdam, the Netherlands); there were 74 MenB cases on average per year in the study period 2015-2019. Case-fatality rate (3.8%) and percentage of patients discharged with sequelae (46%) were derived from literature. Direct costs included treatment costs of the acute phase, long-term sequelae, and public health response. Indirect costs were calculated using the human capital (HCA) and friction costs (FCA) approaches, in which productivity losses were estimated for patients and parents during the acute and sequelae phases. Costs were discounted by 4% yearly. Estimated costs due to MenB IMD in an annual cohort were €3,094,199 with FCA and €9,480,764 with HCA. Direct costs amounted to €2,974,996, of which 75.2% were related to sequelae. Indirect costs related to sequelae were €52,532 with FCA and €5,220,398 with HCA. Our analysis reflects the high economic burden of MenB-related IMD in the Netherlands. Sequelae costs represent a high proportion of the total costs. Societal costs were dependent on the applied approach (FCA or HCA).

Pediatric central nervous system infections in the Amazon: clinical and laboratory profiles.

Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections. We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology. Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus, Cytomegalovirus, Varicella-zoster virus, Epstein-Barr virus, and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2. Patients with viral infections showed altered levels of consciousness (p = 0.001) when compared to bacterial infections. This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus.

Bioinformatics Analysis of Global Diversity in Meningococcal Vaccine Antigens over the Past 10 Years: Vaccine Efficacy Prognosis.

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains.

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines.

Glycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in E. coli with eight individual amino acid mutations to inactivate three toxin functions. Previous studies in mice showed that 8MTT elicits a strong IgG response, confers protection, and can be used as a carrier protein. Here, we compared 8MTT to traditional carrier proteins TT and cross-reactive material 197 (CRM197), using different polysaccharides as models: Group A Streptococcus cell-wall carbohydrate (GAC), Salmonella Typhi Vi, and Neisseria meningitidis serogroups A, C, W, and Y. The persistency of the antibodies induced, the ability of the glycoconjugates to elicit booster response after re-injection at a later time point, the eventual carrier-induced epitopic suppression, and immune interference in multicomponent formulations were also evaluated. Overall, immunogenicity responses obtained with 8MTT glycoconjugates were compared to those obtained with corresponding TT and, in some cases, were higher than those induced by CRM197 glycoconjugates. Our results support the use of 8MTT as a good alternative carrier protein for glycoconjugate vaccines, with advantages in terms of manufacturability compared to TT.

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.

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network.

In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (-0.12%/month, 95% CI: -0.17 to -0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (-0.43%/month, 95% CI: -0.53 to -0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (-0.9%/month, 95% CI: -1.6 to -0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3-0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

Structured Benefit-Risk Assessment of a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals Ages 12 Months and Older.

A favorable benefit-risk balance is required to support licensure of biologics, in keeping with regulatory agencies' evolving recommendations, including the United States Food and Drugs Administration. We present a structured semi-quantitative benefit-risk analysis of MenACYW-TT, a quadrivalent meningococcal conjugate vaccine against Neisseria meningitidis serogroups, A, C, W and Y versus licensed comparators in individuals aged ≥ 12 months. We used data from six MenACYW-TT clinical trials, stratified by age group, versus licensed vaccines: toddlers (12-23 months; Nimenrix® [MCV4-TT]), children (2-9 years; Menveo® [MCV4-CRM]), adolescents (10-17 years; MCV4-CRM or Menactra® [MCV4-DT]), adults (18-55 years; MCV4-DT) and older adults (≥ 56 years; Menomune®-A/C/Y/W-135 [MPSV4]). Eight benefit (seroresponse and seroprotection for A, C, W and Y) and five risk outcomes (any and grade 3 solicited injection site and systemic reactions, and serious adverse events) were measured at Day 30 after initial vaccination. Analyses were conducted by baseline vaccination status (meningococcal vaccine-naïve or vaccine-primed). MenACYW-TT showed favorable seroresponse and seroprotection among vaccine-naïve participants aged ≥ 2years, against all serogroups, compared with MCV4-CRM, MCV4-DT and MPSV4. In vaccine-naïve toddlers, there was a favorable effect for serogroup C, but no difference between MenACYW-TT and MCV4-TT for serogroups A, Y and W. A favorable effect for MenACYW-TT against serogroup C was observed in all vaccine-naïve and combined vaccine-naïve and MenC conjugate vaccine-primed groups. For all risk criteria, there were no differences between MenACYW-TT and MCV4s in toddlers, children, adolescents and adults. Results for solicited injection site and systemic reactions favored MPSV4 in older adults. The benefit-risk profile for MenACYW-TT showed favorable seroresponse and seroprotection in individuals aged ≥ 2 years and no difference in risk criteria between MenACYW-TT and MCV4s. MenACYW-TT may provide an alternative to the standard-of-care for meningococcal disease prevention in those aged ≥ 12 months.

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.