Invasive Meningococcal Disease Research Articles

Meningococcal B Immunisation in Adults and Potential Broader Immunisation Strategies: A Narrative Review.

Recombinant vaccines against invasive meningococcal disease due to Neisseria meningitidis serogroup B (MenB) have shown substantial impact in reducing MenB disease in targeted populations. 4CMenB targets four key N. meningitidis protein antigens; human factor H binding protein (fHbp), Neisserial heparin binding antigen (NHBA), Neisseria adhesin A (NadA) and the porin A protein (PorA P1.4), with one or more of these expressed by most pathogenic MenB strains, while MenB-FHbp targets two distinct fHbp variants. While many countries recommend MenB immunisation in adults considered at high risk due to underlying medical conditions or immunosuppression, there are no recommendations for routine use in the general adult population. We reviewed the burden of MenB in adults, where, while incidence rates remain low (and far lower than in young children<5years of age at greatest risk), a substantial proportion of MenB cases (20% or more) is now observed in the adult population; evident in Europe, Australia, and in the United States. We also reviewed immunogenicity data in adults from clinical studies conducted during MenB vaccine development and subsequent post-licensure studies. A 2-dose schedule of 4CMenB generates hSBA titres≥1:4 towards all four key vaccine target antigens in up to 98-100% of subjects. For MenB-FHbp, a≥fourfold rise in hSBA titres against the four primary representative test strains was observed in 70-95% of recipients following a 3-dose schedule. While this suggests potential benefits for MenB immunisation if used in adult populations, data are limited (especially for adults>50years) and key aspects relating to duration of protection remain unclear. Although a broader adult MenB immunisation policy could provide greater protection of the adult population, additional data are required to support policy decision-making.

Meningococcal Antibiotic Resistance: Molecular Characterization of Isolates from Patients with Invasive Meningococcal Disease (IMD) in Greece.

For effective case management and chemoprophylaxis of Invasive Meningococcal Disease (IMD), prompt antibiotic treatment is required. N. meningitidis is usually susceptible to antibiotics, but reduced susceptibility to penicillin, ciprofloxacin, and rifampicin is increasing worldwide, jeopardizing patients' outcome. We assessed, phenotypically and genotypically, the antimicrobial resistance patterns of 192 strains isolated from IMD cases from all over Greece during 2010-2021. Antimicrobial susceptibility to penicillin, rifampicin, and ciprofloxacin was determined using the E-test. All isolates were genotyped by Multilocus Sequence Typing (MLST). penA, rpoB, and gyrA genes were amplified by PCR and sequenced. Of the 192 isolates, 37% (72/192) were penicillin-susceptible/had increased exposure, and 11% (21/192) were penicillin-resistant. Among those, 40 penA alleles were identified; penA1, penA27, and penA3 were highly associated with susceptibility to penicillin; penA14, penA25, and penA22 related to reduced susceptibility to penicillin, while penA9, penA910, and penA295 had resistance to penicillin. Two ciprofloxacin-resistant isolates harbored the gyrA346 allele, while one rifampicin-resistant isolate harbored the rpoB5 allele. Resistance to ciprofloxacin and rifampicin remains rare. As Greece is one of the countries with high antimicrobial resistance, continued monitoring of antibiotic resistance is important to ensure timely detection of emerging resistance for treatment and prevention guidelines.

Invasive Meningococcal Disease in Children - A literature Review

Invasive Meningococcal Disease in Children - A literature Review

Excess mortality among people with communicable diseases over a 30-year period, Victoria, Australia: a whole of population cohort study

Understanding mortality burden associated with communicable diseases is key to informing resource allocation, disease prevention and control efforts, and evaluating public health interventions. We quantified excess mortality among people notified with communicable diseases in Victoria, Australia. Cases of communicable disease notified in Victoria between 1 January 1991 and 31 December 2021 were linked to the death registry. Informational gain obtained through linkage and 30-day case fatality rates were calculated for each disease. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated up to a year following illness onset. There were 1,032,619 cases and 5985 (0.58%) died ≤30 days of illness onset. Following linkage, the 30-day case fatality rate increased more than 2-fold. Diseases with high 7-day SMR signifying excess mortality included invasive pneumococcal disease (167.7, 95% CI 153.4-182.7); listeriosis (166.2, 95% CI 121.2-218.3); invasive meningococcal disease (145.9, 95% CI 116.7-178.3); legionellosis (43.3, 95% CI 28.0-62.0); and COVID-19 (21.9, 95% CI 19.7-24.3). Most diseases exhibited a strong negative gradient, with high SMRs in the first 7-days of illness onset that reduced over time. We demonstrated that the rate of death in Victoria's notifiable disease surveillance dataset is underestimated. Further, compared to a general population, there is evidence of elevated all-cause mortality among people notified with communicable diseases often up to one year following illness onset. Not all elevated risk is likely directly attributable to the communicable diseases of interest, rather, it may reflect underlying comorbidities or behaviours in these individuals. Regardless of attribution, infection with communicable diseases may represent a marker of mortality. Key to preventing deaths may be through timely and appropriate transition to primary and preventive healthcare following diagnosis. No funding was provided for this study.

Calendario de vacunaciones del adolescente. Consenso AEV, CAV-AEP y SEMA

We present the consensus document on the immunization schedule for adolescents developed by 3 scientific societies: the Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines (CAV-AEP), the Spanish Society of Adolescent Medicine (SEMA) and the Spanish Association of Vaccinology (AEV). There are particularities in infectious disease during adolescence, such as an increased susceptibility to pertussis, poorer outcomes of chickenpox, mumps and hepatitis A, a high incidence of sexually transmitted infections or increased prevalence of meningococcal carriage. The document analyses the schedule for adolescents in the context of vaccination policy overall. It contemplates the vaccines to be included in the immunization schedule for healthy adolescents: against invasive meningococcal disease (tetravalent ACWY and B), against human papillomavirus (which should be gender-neutral), against pertussis, against influenza and against SARS-CoV-2 (in unvaccinated individuals and at-risk groups). It is worth noting that the 4CMenB vaccine appears to confer some protection against gonococcal infection, which would be a considerable added value for adolescents. The vaccination of adolescents belonging to risk groups or travelling abroad also needs to be contemplated, as is the case in any other age group. Vaccination against hepatitis A, which is included in the routine immunization schedule of Catalonia, Ceuta and Melilla from the second year of life, should also be considered a priority in adolescents traveling to endemic areas.

Analysis of Intestinal and Nasopharyngeal Microbiota of Children with Meningococcemia in Pediatric Intensive Care Unit: INMACS-PICU Study.

Microbiota composition might play a role in the pathophysiology and course of sepsis, and understanding its dynamics is of clinical interest. Invasive meningococcal disease (IMD) is an important cause of community-acquired serious infection, and there is no information regarding microbiota composition in children with meningococcemia. In this study, we aimed to evaluate the intestinal and nasopharyngeal microbiota composition of children with IMD. Materials and Methods: In this prospective, multi-center study, 10 children with meningococcemia and 10 age-matched healthy controls were included. Nasopharyngeal and fecal samples were obtained at admission to the intensive care unit and on the tenth day of their hospital stay. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. Results: Regarding the alpha diversity on the day of admission and on the tenth day at the PICU, the Shannon index was significantly lower in the IMD group compared to the control group (p = 0.002 at admission and p = 0.001, on the tenth day of PICU). A statistical difference in the stool samples was found between the IMD group at Day 0 vs. the controls in the results of the Bray-Curtis and Jaccard analyses (p = 0.005 and p = 0.001, respectively). There were differences in the intestinal microbiota composition between the children with IMD at admission and Day 10 and the healthy controls. Regarding the nasopharyngeal microbiota analysis, in the children with IMD at admission, at the genus level, Neisseria was significantly more abundant compared to the healthy children (p < 0.001). In the children with IMD at Day 10, genera Moraxella and Neisseria were decreased compared to the healthy children. In the children with IMD on Day 0, for paired samples, Moraxella, Neisseria, and Haemophilus were significantly more abundant compared to the children with IMD at Day 10. In the children with IMD at Day 10, the Moraxella and Neisseria genera were decreased, and 20 different genera were more abundant compared to Day 0. Conclusions: We first found alterations in the intestinal and nasopharyngeal microbiota composition in the children with IMD. The infection itself or the other care interventions also caused changes to the microbiota composition during the follow-up period. Understanding the interaction of microbiota with pathogens, e.g., N. meningitidis, could give us the opportunity to understand the disease's dynamics.

PCR141 What Drives the Views of Young People (16–23 YEARS) and Parents on Invasive Meningococcal Disease and Their Willingness to Vaccinate?

To explore factors driving young peoples’ and parents’ views on invasive meningococcal disease (IMD) and their willingness to vaccinate (WTV).

Hypervirulent Strains of Neisseria meningitidis and Clinical Manifestations in Children With Invasive Meningococcal Disease.

Hypervirulent clonal complex (cc) have been associated with higher incidence and case fatality rate of invasive meningococcal disease (IMD). The aim of this study was to describe the clinical manifestations of the hypervirulent cc of meningococcus in children. Retrospective study in patients hospitalized by IMD microbiologically confirmed at three children's tertiary health care centers in Santiago, Chile, between 2010 and 2018. Demographic, clinical information and determination of the cc and factor H binding protein (fHbp) alleles were performed. In total 93 cases were evaluated, sequence typing was available for 91 cases, and 87 (95.6%) had a cc assigned; 63.7% were MenW and 31.8% MenB. The median age was 9 months, 67% were male and 18.7% had any comorbidity. A 26.4% presented neurological deficit, 25.3% petechiae and 20% diarrhea. Sixty-seven percent were admitted to the pediatric intensive care unit (PICU) and the case fatality rate was 9.9%. Regarding cc and fHbp alleles, ST11, ST41/44 and allele 22 were the most frequently identified, with 63.7%, 19.8% and 72.5%, respectively. We found statistically significant differences between the cc and presence of petechiae, diagnosis of meningococcemia plus meningitis, admission and days in PICU and advanced support. Allele 22 for fHbp was associated with the absence of petechiae, low suspicion of IMD, less diagnosis of meningitis+meningococcemia, PICU admission, advanced support and adrenal insufficiency. Epidemiological and microbiological surveillance of IMD should integrate clinical and laboratory components, including molecular and genetic characterization, to enrich the dynamic understanding of the clinical evolution of IMD.

EPH258 Assessing Different Combinations of 4CMENB and Menacwy-CRM197 Vaccines in Infants, Toddlers and Adolescents of Argentina to Maximize Its Impact Against Invasive Meningococcal Disease

EPH258 Assessing Different Combinations of 4CMENB and Menacwy-CRM197 Vaccines in Infants, Toddlers and Adolescents of Argentina to Maximize Its Impact Against Invasive Meningococcal Disease

Recent Evolution of Susceptibility to Beta-Lactams in Neisseria meningitidis.

Beta-lactams are the main antibiotics for the treatment of invasive meningococcal disease. However, reduced susceptibility to penicillin G is increasingly reported in Neisseria meningitidis and reduced susceptibility to third-generation cephalosporines (3GC) and the rare acquisition of ROB-1 beta-lactamase were also described. Modifications of penicillin-binding protein 2 (PBP2) encoded by the penA gene are the main described mechanism for the reduced susceptibility to penicillin and to other beta-lactams. penA modifications were analyzed using the sequences of all penA genes from cultured isolates between 2017-2021 in France (n = 1255). Data showed an increasing trend of reduced susceptibility to penicillin from 36% in 2017 to 58% in 2021. Reduced susceptibility to 3GC remained limited at 2.4%. We identified 74 different penA alleles and penA1 was the most frequent wild-type allele and represented 29% of all alleles while penA9 was the most frequently altered allele and represented 17% of all alleles. Reduced susceptibility to 3GC was associated with the penA327 allele. The amino acid sequences of wild-type and altered PBP2 were modeled. The critical amino acid substitutions were shown to change access to the active S310 residue and hence hinder the binding of beta-lactams to the active site of PBP2.

Epidemiology of invasive meningococcal disease and its sequelae: a population-based study in Italian primary care, 2000-2019.

Invasive meningococcal disease (IMD) is a severe infectious disease. Although effective preventive and therapeutical strategies are available, the fatality rate remains high in the general population, with an occurrence of meningococcal-related severe sequelae involving 10-20% of survivors. Given the crucial role of general practitioners in recognizing and preventing IMD and its related sequelae, we aim to assess the burden of these conditions in primary care. Using an Italian primary care database, the incidence rate of IMD was calculated in the period 2000-2019 by capturing the first diagnosis registered during follow-up. As far as meningococcal-related sequelae are concerned, we identified and clinically evaluated each potential sequela during the first 3 months, from 3 to 12 months, and up to 36 months. Among 508 patients diagnosed with IMD, 403 (incidence rate: 0.24 per 10,000 person-years) comprised those diagnosed with IMD in patients aged 15 years or older. We ascertained 104 sequelae (20.4%); 76% of them occurred in those aged 25 or older; 42, 27, and 35 were assessed as short-, medium-, or long-term sequelae, respectively. Overall, 4.7% of IMD patients reported physical sequelae, while 12.2% and 5.7% of patients reported neurological and psychological sequelae, respectively. Our study showed that a substantial proportion of IMD and related sequelae occur in individuals aged over 25, with a non-negligible burden for healthcare systems. As for the paediatric population, effective communication on the relevance of meningococcal vaccination in adults should be proficiently fostered.

Adolescent and parental decision-making for the MenACWY vaccination: influential predictors and parental-adolescent differences among households in the Netherlands

BackgroundBetween 2015 and 2018 The Netherlands experienced increases of invasive meningococcal disease (IMD) serogroup W (MenW). Therefore in 2018 the MenACWY vaccination was introduced in the National Immunisation Programme (NIP) and a catch-up campaign was initiated targeting adolescents.This study aimed to gain insight into what factors played a role in the decision-making process regarding the MenACWY vaccination. The focus was on the differences in the decision-making of parents and adolescents in order to assess what factors influence the decisions made.MethodsAn online questionnaire was offered to adolescents and one of their parents. We used random forest analyses to determine which factors best predict the outcome of the MenACWY vaccination decision. We carried out ROC (receiver-operator characteristics) analyses to confirm the predictive value of the variables.ResultsAmong parents several factors stand out, centring on the process of the decision, their attitude about the MenACWY vaccination, trust in the vaccination, and ideas of important people around them. Among adolescents the three stand-out predictors are the ideas of important people around them, the process of the decision and trust in the vaccination.Parents have prominent influence in the decision-making, while the adolescent’s influence in the household decision-making is more limited. Adolescents tend to be less engaged and spend less time thinking about the decision compared to parents. Opinions of parents and adolescents from the same households concerning the factors that are influential do not differ a lot in the final decision-making.ConclusionsInformation about MenACWY vaccination might be mainly addressed to the parents of the adolescents and whereby the dialogue about MenACWY vaccination between parents and adolescents will be stimulated. With regard to the predictor trust in vaccination, raising the frequency of use of certain sources, especially those deemed very reliable among households such as conversations with a GP or the provider of the vaccination (GGD/JGZ), might prove a useful strategy to solidify vaccination uptake numbers.

The propositive study: Immunogenicity and safety of a four-component recombinant protein-based vaccine against MenB and a quadrivalent conjugate MenACWY vaccine in people living with HIV.

People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely recommended to all people living with HIV, but no study has yet assessed the immunogenicity and safety of a meningococcal serogroup B vaccine or the co-administration of a MenB and MenACWY vaccine in people living with HIV. This phase IV open-label clinical trial investigated the immunogenicity and safety of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in a population of people living with HIV. Immunogenicity analysis was performed before vaccination and 1 month after the second doses of 4CMenB and MenACWY. Primary outcome measures were serum bactericidal assay geometric mean titres against three MenB reference strains at baseline and 1 month post vaccination, the proportion of participants achieving a putative protective titre of ≥4, and the proportion of participants with a ≥4-fold rise in titre from baseline. Secondary outcome measures were serum bactericidal assay geometric mean titres against MenA, C, W, and Y reference strains at baseline and 1 month post vaccination, the proportion achieving a putative protective titre of ≥8, and the proportion with a ≥4-fold rise in titre from baseline. Safety outcomes were solicited and unsolicited adverse events in the 7 days following vaccination. The trial was registered with clinicaltrials.gov (NCT03682939). In total, 55 participants aged 20-45 years were enrolled. All participants (100%; 95% confidence interval [CI] 93-100) achieved putative protective titres for two of the three MenB strains and for MenA, W, and Y. A total of 98% (95% CI 89-100) achieved a protective titre for the third MenB strain and 94% (95% CI 83-99) for MenC. No serious adverse events were reported. 4CMenB and MenACWY were immunogenic and well-tolerated in a population of people living with HIV 1 month after two doses.

Invasive meningococcal disease in Norway in the two decades before the COVID-19 pandemic

ObjectivesDisease caused by the bacterium Neisseria meningitidis remains a worldwide public health challenge, despite the steadily decreasing incidence in Western countries. The objective of this study was to explore the epidemiology of invasive meningococcal disease in Norway over the last two decades. DesignAll isolates sent to the National Reference Laboratory from patients with invasive meningococcal disease between the years 2000 and 2019 were analyzed using whole genome sequencing (total: 625). ResultsA five-fold decrease in case numbers occurred over this period, and the situation has gone from being dominated by serogroup B to one where serogroups Y and W are more prevalent. Concurrently, the mean age at infection has increased from 18 to 33 years. Among the 350 serogroup B isolates, 87% were an exact match or cross-reactive with one or both the currently available serogroup B vaccines, but the proportion decreased in the past decade. Core genome analyses revealed a high variation in the number of allelic differences accumulated in epidemiologically linked isolates to the point that near-identical isolates were found several years apart. ConclusionAllelic distance is an imprecise metric for the degree of epidemiologic linkage between isolates in N. meningitidis.

The burden of invasive meningococcal disease in the Netherlands, 2011-2020.

Representative information on disease course and outcome of invasive meningococcal disease (IMD) is important because of the shift in meningococcal epidemiology that recently occurred in the Netherlands. With this study, we update earlier research on the burden of IMD in the Netherlands. We performed a retrospective study using Dutch surveillance data on IMD from July 2011 to May 2020. Clinical information was collected from hospital records. The effect of age, serogroup, and clinical manifestation on disease course and outcome was assessed in multivariable logistic regression analyses. Grouping of infecting isolates was performed by Ouchterlony gel diffusion or by PCR. Clinical information was collected for 278 IMD cases of which the majority had IMD-B (55%), followed by IMD-W (27%), IMD-Y (13%), and IMD-C (5%). Most patients presented with meningitis (32%) or sepsis (30%). Hospitalisation for≥10days was most frequent among 24-64year olds (67%). ICU admission was highest among 24-64year olds (60%), and in case of sepsis (70%), or sepsis plus meningitis (61%). Sequelae at discharge was lower for patients with mild meningococcaemia compared to patients with sepsis plus meningitis (OR: 0.19, 95% CI: 0.07-0.51). The overall case fatality rate was 7%, and was highest for IMD-Y (14%) and IMD-W (13%) patients. IMD remains a disease with high morbidity and mortality. Sepsis (with or without meningitis) is associated with a more severe disease course and outcome compared to other clinical manifestations. The high disease burden can be partly prevented by meningococcal vaccination.

Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004–2020

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Māori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Māori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Whole genome analysis of Neisseria meningitidis isolates from invasive meningococcal disease collected in the Czech Republic over 28 years (1993-2020).

Invasive meningococcal disease belongs among the most dangerous infectious diseases in the world. Several polysaccharide conjugate vaccines against serogroups A, C, W and Y are available and two recombinant peptide vaccines against serogroup B (MenB vaccines) have been developed: MenB-4C (Bexsero) and MenB-fHbp (Trumenba). The aim of this study was to define the clonal composition of the Neisseria meningitidis population in the Czech Republic, to determine changes in this population over time and to estimate the theoretical coverage of isolates by MenB vaccines. This study presents the analysis of whole genome sequencing data of 369 Czech N. meningitidis isolates from invasive meningococcal disease covering 28 years. Serogroup B isolates (MenB) showed high heterogeneity and the most common clonal complexes were cc18, cc32, cc35, cc41/44, and cc269. Isolates of clonal complex cc11 were predominately serogroup C (MenC). The highest number of serogroup W isolates (MenW) belonged to clonal complex cc865, which we described as exclusive to the Czech Republic. Our study supports the theory that this cc865 subpopulation originated in the Czech Republic from MenB isolates by a capsule switching mechanism. A dominant clonal complex of serogroup Y isolates (MenY) was cc23, which formed two genetically quite distant subpopulations and which showed constant representation throughout the observed period. The theoretical coverage of isolates by two MenB vaccines was determined using the Meningococcal Deduced Vaccine Antigen Reactivity Index (MenDeVAR). Estimated Bexsero vaccine coverage was 70.6% (for MenB) and 62.2% (for MenC, W, Y). For Trumenba vaccine, estimated coverage was 74.6% (for MenB) and 65.7% (for MenC, W, Y). Our results demonstrated sufficient coverage of Czech heterogeneous population of N. meningitidis with MenB vaccines and, together with surveillance data on invasive meningococcal disease in the Czech Republic, were the basis for updating recommendations for vaccination against invasive meningococcal disease.

Neisseria meningitidis Sibling Small Regulatory RNAs Connect Metabolism with Colonization by Controlling Propionate Use.

Neisseria meningitidis (meningococcus) colonizes the human nasopharynx, primarily as a commensal, but sporadically causing septicemia and meningitis. During colonization and invasion, it encounters different niches with specific nutrient compositions. Small noncoding RNAs (sRNAs) are used to fine-tune expression of genes, allowing adaptation to their physiological differences. We have previously characterized sRNAs (Neisseria metabolic switch regulators [NmsRs]) controlling switches between cataplerotic and anaplerotic metabolism. Here, we extend the NmsR regulon by studying methylcitrate lyase (PrpF) and propionate kinase (AckA-1) involved in the methylcitrate cycle and serine hydroxymethyltransferase (GlyA) and 3-hydroxyacid dehydrogenase (MmsB) involved in protein degradation. These proteins were previously shown to be dysregulated in a ΔnmsRs strain. Levels of transcription of target genes and NmsRs were assessed by reverse transcriptase quantitative PCR (RT-qPCR). We also used a novel gene reporter system in which the 5' untranslated region (5' UTR) of the target gene is fused to mcherry to study NmsRs-target gene interaction in the meningococcus. Under nutrient-rich conditions, NmsRs downregulate expression of PrpF and AckA-1 by direct interaction with the 5' UTR of their mRNA. Overexpression of NmsRs impaired growth under nutrient-limiting growth conditions with pyruvate and propionic acid as the only carbon sources. Our data strongly suggest that NmsRs downregulate propionate metabolism by lowering methylcitrate enzyme activity under nutrient-rich conditions. Under nutrient-poor conditions, NmsRs are downregulated, increasing propionate metabolism, resulting in higher tricarboxylic acid (TCA) activities. IMPORTANCE Neisseria meningitidis colonizes the human nasopharynx, forming a reservoir for the sporadic occurrence of epidemic invasive meningococcal disease like septicemia and meningitis. Propionic acid generated by other bacteria that coinhabit the human nasopharynx can be utilized by meningococci for replication in this environment. Here, we showed that sibling small RNAs, designated NmsRs, riboregulate propionic acid utilization by meningococci and, thus, colonization. Under conditions mimicking the nasopharyngeal environment, NmsRs are downregulated. This leads to the conversion of propionic acid to pyruvate and succinate, resulting in higher tricarboxylic acid cycle activity, allowing colonization of the nasopharynx. NmsRs link metabolic state with colonization, which is a crucial step on the trajectory to invasive meningococcal disease.

Invasive Meningococcal Disease and Meningococcal Serogroup B Vaccination in Adults and Their Offspring: Knowledge, Attitudes, and Practices in Italy (2019).

Despite its effectiveness in preventing invasive meningococcal disease (IMD), pediatric uptake of recombinant meningococcal vaccination for serogroup B meningitis (MenB) is low in Italy. This study aimed to investigate knowledge, attitudes, and practice (KAP) about IMD and the vaccine uptake for MenB from July to December 2019, in a sample collected from a series of local Facebook discussion groups from the provinces of Parma and Reggio Emilia (North-Eastern Italy; 337,104 registered users). A self-administered anonymous web-based questionnaire was used to collect demographics, knowledge status, perceived risk for contracting meningitis, attitude towards the utility of meningococcal vaccine, and willingness to receive/perform MenB vaccine in their offspring. In total, 541 parents returned a fully completed questionnaire (response rate of 1.6% of potential recipients), with a mean age of 39.2 years ± 6.3 (78.1% females). Meningococcal infection was identified as severe or highly severe by most participants (88.9%), while it was recognized as being frequent/highly frequent in the general population by 18.6% of respondents. The overall knowledge status was unsatisfactory (57.6% ± 33.6 of correct answers to the knowledge test). Even though 63.4% of participants were somewhat favorable to MenB/MenC vaccines, offspring's vaccination towards MenB was reported by only 38.7% of participants. In a binary logistic regression model, the male gender of respondents (adjusted odds ratio [aOR] 3.184, 95% confidence interval [95%CI] 1.772 to 5.721), living in a municipality >15,000 inhabitants (aOR 1.675, 95%CI 1.051 to 2.668), reporting a favorable attitude on meningococcus B vaccine (aOR 12.472, 95%CI 3.030 to 51.338), having been vaccinated against serogroup B (aOR 5.624, 95%CI 1.936 to 16.337) and/or serogroup C (aOR 2.652, 95%CI 1.442 to 4.872), and having previously vaccinated their offspring against serogroup C meningococcus (aOR 6.585, 95%CI 3.648 to 11.888) were characterized as positive effectors of offspring's vaccination. On the contrary, having a higher risk perception on vaccines was identified as the only negative effector (aOR 0.429, 95%CI 0.241 to 0.765). Our results hint towards extensive knowledge gaps on IMD and preventive interventions in the general population, suggesting that a positive attitude towards vaccines and vaccinations could be identified as the main effector also for MenB acceptance. Interventions in the general population aimed at improving confidence, compliance, and acknowledgment of the collective responsibility, as well as preventing actual constraints and the sharing of false beliefs on infectious diseases and their preventive measures, could therefore increase vaccination acceptance in both targeted individuals and their offspring.

159. Knowledge of Invasive Meningococcal Disease and Vaccination Recommendations for Adolescents and Young Adults among US Physicians

159. Knowledge of Invasive Meningococcal Disease and Vaccination Recommendations for Adolescents and Young Adults among US Physicians