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.

Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Investigation of a bacterial meningitis cluster in a refugee settlement, Obongi District, Uganda, March 2023.

On 6 March 2023, Neisseria meningitidis serogroup C was isolated from a cerebral spinal fluid sample from Obongi District, Uganda. This sample was one of many from patients who were presenting with fever, convulsions, and altered consciousness. We investigated to determine the scope of the meningitis cluster, identify risk factors of contracting meningitis, and inform control measures. We reviewed medical records, conducted active community case finding, and conducted key informant interviews in the affected communities to identify cases and factors associated with contracting meningitis. We analysed case data by person, place, and time. Between 22 December 2022 and 1 May 2023, 25 cases with 2 deaths of bacterial meningitis occurred in Palorinya Refugee Settlement, Obongi District. Of these, 4 were laboratory-confirmed with Neisseria meningitidis serogroup C, 6 were probable cases, and 15 were suspected cases. Most (76%) of case-patients were <18 years old with a median age of 12 years (range 1-66 years). None of the case-patients was vaccinated against Neisseria meningitidis serogroup C. Each case-patient was from a different household and there was no epidemiological link between any of the cases. This meningococcal meningitis cluster caused by Neisseria meningitidis serogroup C occurred among non-vaccinated persons mostly aged <18 years in Palorinya Refugee Settlement. We recommended vaccination of at-risk persons.

Awareness, attitudes, and practices on meningococcal serogroup B vaccination in the United States among parents of older adolescents and among young adults.

OBJECTIVE: Meningococcal serogroup B (MenB) vaccination is recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents and young adults 16-23-years-old under shared clinical decision-making (SCDM). However, MenB vaccination coverage in this population remains low in the United States (US). We investigated the awareness, attitudes, and practices regarding MenB disease and vaccination among parents of 16-18-year-old older adolescents and among 19-23-year-old young adults. METHODS: An online survey was conducted in September-October 2022 among parents of older adolescents and among young adults recruited from a US-based patient panel. RESULTS: There were 606 total participants, including parents of MenB-vaccinated (n = 151) and non-vaccinated (n = 154) adolescents, and also MenB-vaccinated (n = 150) and non-vaccinated (n = 151) young adults. Non-vaccinated cohorts reported low awareness of MenB disease (58.3-67.5%) and vaccination (49.7-61.0%), though awareness was higher among non-vaccinated parents. However, all cohorts reported high interest in learning more about MenB disease and vaccination. Vaccinated cohorts relied on primary care providers (PCPs) to initiate MenB vaccination conversation and had a low awareness of SCDM at 35.1-45.3%, though those aware of SCDM were more likely to participate in decision-making. Barriers to MenB vaccination included lack of PCP recommendation, vaccine side effects, and uncertainty about vaccination need. CONCLUSIONS: There are gaps in awareness of MenB disease, vaccination, and SCDM among parents and patients in the US, resulting in missed opportunities for discussing and administering MenB vaccination. Targeted education on MenB and vaccination recommendations may increase these opportunities and improve MenB vaccination awareness and initiation.

MenB disease, a type of meningitis, is a serious and life-threatening illness. The US Centers for Disease Control and Prevention (CDC) recommends that 16­23-year-olds get a MenB vaccine after talking with their healthcare provider and deciding it is the right choice. As of 2021, only about 3 in 10 17-year-olds had received a MenB vaccine. In this study, we used an online survey to learn about parents of older teens' (16­18-years-old) and young adults' (19­23-years-old) awareness, thoughts, and practices related to meningitis and the MenB vaccine. Parents of non-vaccinated teens, and non-vaccinated young adults, had a lower awareness of the causes, risks, and symptoms of meningitis, and the MenB vaccine. In addition, most parents thought the impact of meningitis would be severe, compared with young adults who thought it would be less severe. Most participants were also not aware of their role in deciding if they or their child should be vaccinated against MenB. However, most showed a high interest in learning more about meningitis and the MenB vaccine. We also found that most teens and young adults who did receive the MenB vaccine received it right after talking about it with their healthcare provider. These findings show a clear opportunity to address gaps in awareness and thoughts about meningitis and MenB vaccination. Providing education and resources to parents, young adults, and healthcare providers could create more opportunities to discuss MenB vaccination and lead to more teens and young adults accessing vaccination and being protected against meningitis.

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

Introducción: La principal medida de prevención frente a la enfermedad meningocócica invasiva es la vacunación. El objetivo de este estudio es evaluar la aceptabilidad y las desigualdades socioeconómicas en el acceso a la vacuna frente a meningococo B (MenB) en la Comunidad de Madrid en el periodo previo a la introducción de la misma en el calendario. Materiales y métodos: Se realizó un estudio observacional descriptivo en la cohorte de niños/as nacidos entre 2016 y 2019, de tipo ecológico, empleando registros poblacionales electrónicos. Se describieron las coberturas de vacunación, se analizaron los factores asociados al estado vacunal, se describieron las distribuciones espaciales de cobertura de vacunación y de índice de privación (IP) y se analizó la asociación entre ambas mediante regresión espacial. Resultados: Se observó una tendencia creciente de las coberturas de primovacunación, pasando de un 44% en la cohorte de nacidos en el año 2016 a un 68% en la cohorte de 2019. Se encontró asociación estadísticamente significativa entre el estado vacunal y el IP (OR de primovacunación en zonas con IP5 respecto a zonas con IP1: 0,38; IC 95%: 0,39-0,50; p<0,001). El análisis espacial mostró correlación inversa entre el IP y la cobertura de vacunación. Conclusiones: El ascenso de las coberturas de esta vacuna muestra aceptación por parte de la población. La relación entre nivel socioeconómico y cobertura de vacunación confirma la existencia de una desigualdad en salud, y subraya la importancia de su inclusión en el calendario.(AU)

Introduction: The 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 methods: We 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. Results: We 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. Conclusions: The 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.(AU)

The meningitis outbreak returns to Niger: Concern, efforts, challenges, and recommendations.

Meningitis, a disease that commonly manifests in African meningitis belt, continues to be a public health problem as it is a fatal disease that leave survivors with long-term effects. Most cases of meningitis are due to bacterial and viral infection, although parasites, fungus, cancer, drugs, and immune disorders can rarely cause meningitis. Stiff neck, high temperature, light sensitivity, disorientation, headaches, and vomiting are the most typical symptoms of meningitis. Niger, being in African meningitis belt, has been affected by many meningitis outbreaks. Since 2015, a total of 20,789 cases and 1369 fatalities (CFR 6.6%) have been documented in Niger. In contrast to earlier seasons, the current outbreak of meningitis in Niger exhibits both an increase in the number of cases and a rise in the growth rate. A total of 559 cases of meningitis, including 18 fatalities (overall CFR 3.2%), were reported in the Zinder Region, southeast of Niger, from 1 November 2022 to 27 January 2023, compared to 231 cases reported from 1 November 2021 to 31 January 2022. In the current outbreak, the Neisseria meningitidis serogroup C (NmC) is responsible for the majority of laboratory confirmed cases (104/111; 93.7%). To organize the response to the outbreak, a global team of WHO and other partners, including MSF and UNICEF, has been sent to Niger. Even though there are many challenges in battle against meningitis in Niger, immunization, antibiotics administration and strong disease surveillance are recommended techniques to cope with the current meningitis outbreak in Niger.

Trends in Neisseria meningitidis serogroups amongst patients with suspected cerebrospinal meningitis in the meningitis belt of Ghana: a 5-year retrospective study.

BACKGROUND: Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana's meningitis belt. METHODS: Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran-Armitage trend test. RESULTS: Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P < 0.01), and serogroup W showed a downward trend (P < 0.01). However, no significant trend was observed for any other serogroup. CONCLUSION: This study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana's meningitis belt.

[Research progress on immunogenicity evaluation of serogroup B meningococcal vaccine].

Epidemic cerebrospinal meningitis (meningococcal meningitis) is an acute respiratory infectious disease with high mortality and serious sequelae. Meningococcal vaccine is an effective measure to prevent and control meningococcal meningitis. At present, group B meningococcal meningitis has become the main prevalent serum group in the world, including China. Meningococcal ACYW and other vaccines are mainly composed of capsular polysaccharides, while the main component of group B meningococcal vaccine is protein, including outer membrane vesicles (OMV) and recombinant protein vaccine. The methods for evaluating the immunogenicity of group B meningococcal vaccine include hSBA and alternative methods such as meningococcal antigen typing system (MATS), flow cytometric meningococcal antigen surface expression assay (MEASURE), genetic meningococcal antigen typing system (gMATS) and bexsero antigen sequence type (BAST). The evaluation of vaccine immunogenicity is the basis of vaccine development and clinical trial research, However, at present, there is no group B meningococcal vaccine in China. Therefore, in this paper, the research progress of immunogenicity evaluation of group B meningococcal vaccine has been reviewed, in order to provide technical guidance for the research and development of group B meningococcal vaccine, immunogenicity evaluation and clinical trial research in China.

Meningococcal Disease in Pediatric Age: A Focus on Epidemiology and Prevention.

Meningococcal disease is caused by Neisseria meningitidis; 13 serogroups have been identified and differentiated from each other through their capsular polysaccharide. Serotypes A, B, C, W, X, and Y are responsible for nearly all infections worldwide. The most common clinical manifestations are meningitis and invasive meningococcal disease, both characterized by high mortality and long-term sequelae. The infection rate is higher in children younger than 1 year and in adolescents, who are frequently asymptomatic carriers. Vaccination is the most effective method of preventing infection and transmission. Currently, both monovalent meningococcal vaccines (against A, B, and C serotypes) and quadrivalent meningococcal vaccines (against serogroups ACYW) are available and recommended according to local epidemiology. The purpose of this article is to describe the meningococcal vaccines and to identify instruments that are useful for reducing transmission and implementing the vaccination coverage. This aim could be reached by switching from the monovalent to the quadrivalent vaccine in the first year of life, increasing vaccine promotion against ACYW serotypes among adolescents, and extending the free offer of the anti-meningococcal B vaccine to teens, co-administering it with others proposed in the same age group. Greater awareness of the severity of the disease and increased health education through web and social networks could represent the best strategies for promoting adhesion and active participation in the vaccination campaign. Finally, the development of a licensed universal meningococcal vaccine should be another important objective.

Enhancing Meningococcal Genomic Surveillance in the Meningitis Belt Using High-Resolution Culture-Free Whole-Genome Sequencing.

Rollout of meningococcal serogroup A conjugate vaccine in Africa started in 2010, aiming to eliminate meningitis outbreaks, in meningitis belt countries. Since then, studies have been conducted, primarily using isolates, to assess the vaccine impact on the distribution of meningococcal strains in the region. Here, we implemented an innovative, culture-free whole-genome sequencing approach on almost 400 clinical specimens collected between 2017 and 2019 from meningococcal meningitis cases in 6 African countries. About 50% of specimens provided high-quality whole-genome sequence data for comprehensive molecular profiling of the meningococcal pathogen. Three major clonal complexes were identified: CC11 associated with serogroup W, CC181 associated with serogroup X, and CC10217 associated with serogroup C, which continues to rise as a predominant clonal complex in the region. Genomic surveillance for meningococcal meningitis can be significantly improved using culture-free methods to increase data representativeness and monitor changes in epidemiological landscape, especially for countries with low culture rate.

Neisseria meningitidis Serogroup C Clonal Complex 10217 Outbreak in West Kpendjal Prefecture, Togo 2019.

Togo has reported seasonal meningitis outbreaks caused by non-Neisseria meningitidis serogroup A (NmA) pathogens since the introduction of meningococcal serogroup A conjugate vaccine (MACV, MenAfriVac) in 2014. From 2016 to 2017, NmW caused several outbreaks. In early 2019, a NmC outbreak was detected in the Savanes region of Togo and its investigation is described here. Under case-based surveillance, epidemiological and clinical data, and cerebrospinal fluid specimens were collected for every suspected case of meningitis. Specimens were tested for meningitis pathogens using confirmatory microbiological and molecular methods. During epidemic weeks 9 to 15, 199 cases were reported, with 179 specimens being available for testing and 174 specimens (97.2%) were tested by at least one confirmatory method. The NmC was the predominant pathogen confirmed (93.9%), belonging to sequence type (ST)-9367 of clonal complex (CC) 10217. All NmC cases were localized to the West Kpendjal district of the Savanes region with attack rates ranging from 4.1 to 18.8 per 100,000 population and case fatality rates ranging up to 2.2% during weeks 9 to 15. Of the 93 NmC confirmed cases, 63.4% were males and 88.2% were in the 5 to 29 age group. This is the first report of a NmC meningitis outbreak in Togo. The changing epidemiology of bacterial meningitis in the meningitis belt post-MACV highlights the importance of monitoring of emerging strain and country preparedness for outbreaks in the region. IMPORTANCE The recent emergence of an invasive NmC strain in Togo is an example of the changing bacterial meningitis epidemiology in the meningitis belt post-MACV. The current epidemiology includes the regional circulation of various non-NmA serogroups, which emphasizes the need for effective molecular surveillance, laboratory diagnosis, and a multivalent vaccine that is effective against all serogroups in circulation.

Research progress on immunogenicity evaluation of serogroup B meningococcal vaccine / 中华预防医学杂志

Epidemic cerebrospinal meningitis (meningococcal meningitis) is an acute respiratory infectious disease with high mortality and serious sequelae. Meningococcal vaccine is an effective measure to prevent and control meningococcal meningitis. At present, group B meningococcal meningitis has become the main prevalent serum group in the world, including China. Meningococcal ACYW and other vaccines are mainly composed of capsular polysaccharides, while the main component of group B meningococcal vaccine is protein, including outer membrane vesicles (OMV) and recombinant protein vaccine. The methods for evaluating the immunogenicity of group B meningococcal vaccine include hSBA and alternative methods such as meningococcal antigen typing system (MATS), flow cytometric meningococcal antigen surface expression assay (MEASURE), genetic meningococcal antigen typing system (gMATS) and bexsero antigen sequence type (BAST). The evaluation of vaccine immunogenicity is the basis of vaccine development and clinical trial research, However, at present, there is no group B meningococcal vaccine in China. Therefore, in this paper, the research progress of immunogenicity evaluation of group B meningococcal vaccine has been reviewed, in order to provide technical guidance for the research and development of group B meningococcal vaccine, immunogenicity evaluation and clinical trial research in China.

Vaccination information, motivations, and barriers in the context of meningococcal serogroup A conjugate vaccine introduction: A qualitative assessment among caregivers in Burkina Faso, 2018.

BACKGROUND: In March 2017, Burkina Faso introduced meningococcal serogroup A conjugate vaccine (MACV) into the Expanded Programme on Immunization. MACV is administered to children aged 15-18 months, concomitantly with the second dose of measles-containing vaccine (MCV2). One year after MACV introduction, we assessed the sources and content of immunization information available to caregivers and explored motivations and barriers that influence their decision to seek MACV for their children. METHODS: Twenty-four focus group discussions (FGDs) were conducted with caregivers of children eligible for MACV and MCV2. Data collection occurred in February-March 2018 in four purposively selected districts, each from a separate geographic region; within each district, caregivers were stratified into groups based on whether their children were unvaccinated or vaccinated with MACV. FGDs were recorded and transcribed. Transcripts were coded and analyzed using qualitative content analysis. RESULTS: We identified many different sources and content of information about MACV and MCV2 available to caregivers. Healthcare workers were most commonly cited as the main sources of information; caregivers also received information from other caregivers in the community. Caregivers' motivations to seek MACV for their children were driven by personal awareness, engagements with trusted messengers, and perceived protective benefits of MACV against meningitis. Barriers to MACV and MCV2 uptake were linked to the unavailability of vaccines, immunization personnel not providing doses, knowledge gaps about the 15-18 month visit, practical constraints, past negative experiences, sociocultural influences, and misinformation, including misunderstanding about the need for MCV2. CONCLUSIONS: MACV and MCV2 uptake may be enhanced by addressing vaccination barriers and effectively communicating vaccination information and benefits through trusted messengers such as healthcare workers and other caregivers in the community. Educating healthcare workers to avoid withholding vaccines, likely due to fear of wastage, may help reduce missed opportunities for vaccination.