Search Results (158)

Invasive bacterial infections caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis remain a major public health concern. This study aimed to perform the molecular characterization of bacterial strains responsible for meningitis in patients of all ages who met the World Health Organization case definition for meningitis and had cerebrospinal fluid samples collected between January 2021 and December 2022 at the Clinical Bacteriology Laboratory of the National Public Health Institute of Mali. We conducted a surveillance-based observational study using national surveillance data collected between January 2021 and December 2022. Data were collected continuously and in real time throughout the study. The analysis was cross-sectional and descriptive. Data were obtained from samples received at the laboratory, accompanied by individual clinical notification forms. For each sample, demographic data and additional clinical information, including vaccination status, were collected. Infection was diagnosed by isolating invasive strains through culture, confirmed by real-time triplex PCR, and positive cases were further characterized by real-time triplex PCR for serotyping. Overall, 103 infections were confirmed among the 1000 samples received, corresponding to a positivity rate of 10.3%. S. pneumoniae predominated with 62%, followed by H. influenzae type b with 36% and N. meningitidis serogroup X with 2%. The identified serotypes of pneumococcus were predominantly not covered by existing vaccines, particularly serotype 23A (38.30%), while others, including serotypes 1 (17.02%) and 3 (10.63%), are included in the PCV13 vaccine. The distribution of cases by age and gender shows a predominance of males, accounting for 60.2% of cases (62/103). The 0–5 age group is by far the largest, accounting for 76.7% of cases (79/103), with males representing 58. 22% (46 cases). These findings highlight the importance and the need for continuous monitoring surveillance of circulating strains and strengthening vaccination efforts to improve prevention. Full article

Background: The COVID-19 pandemic exposed critical gaps in pandemic preparedness and highlighted the need for vaccine platforms capable of rapid adaptation. Outer membrane vesicle (OMV)-based platforms utilizing vesicles derived from genetically detoxified Neisseria meningitidis serogroup B (Nm-nOMV) represent a promising plug-and-play approach. Methods: This Phase I, first-in-human, randomized, double-blind, placebo- and OMV-controlled trial, evaluated safety, tolerability, and immunogenicity of intranasally administered OMVs combined with SARS-CoV-2 Spike protein in healthy SARS-CoV-2 seropositive adults aged 18–55 years. Forty participants were enrolled across two cohorts: a low-dose cohort receiving 140 μg OMV/70 μg Spike (OMV + Spike, n = 13; OMV alone, n= 3; Placebo, n = 5) and a high-dose cohort receiving 280 μg of OMV/140 μg of Spike (OMV + Spike, n = 13; OMV alone, n = 3; Placebo, n = 3), administered on Days 1 and 22. Safety was assessed through adverse events, vital signs, laboratory parameters, ECG, and pulse oximetry. Immunogenicity was evaluated via systemic SARS-CoV-2 neutralizing antibodies, antigen-specific antibodies (IgG and IgA), and mucosal antibodies (IgA in nasal wash). Results: Intranasal administration of OMVs combined with SARS-CoV-2 Spike protein was safe, well-tolerated, and immunogenic. No serious adverse events were reported, and adverse events were predominantly mild and transient. Dose-dependent increases in systemic and mucosal immune responses were observed, with statistically significant enhanced serum IgG and nasal wash IgA antibodies in the high-dose group. Conclusions: The current clinical data confirm key aspects of the preclinical profile, which demonstrate the potential of the Nm-nOMV platform as a strong adjuvant for mucosal vaccines. These findings support the broader application of the Nm-nOMV vaccine platform in pandemic preparedness. Full article

Background: Invasive meningococcal disease (IMD) remains a rare but severe condition associated with high mortality and a significant risk of long-term sequelae. Despite global vaccination efforts, the epidemiology of Neisseria meningitidis continues to evolve, with serogroup B (MenB) representing the predominant cause of IMD in many high-income countries. Methods: This consensus document reviews current evidence on MenB epidemiology and the role of the multicomponent meningococcal serogroup B vaccine (4CMenB), with a focus on immunogenicity, strain coverage, real-world effectiveness, and remaining challenges. Results: Protein-based MenB vaccines have overcome the limitations of polysaccharide approaches, demonstrating robust immunogenicity across age groups. Real-world data confirm substantial vaccine effectiveness, particularly in infant immunization programs and outbreak settings, with significant reductions in disease incidence. For example, in England in the 3 years after vaccine introduction, MenB IMD incidence declined by 75% in immunized infants compared to unvaccinated controls. Adjusted vaccine efficacy was 52.7% after the two-dose primary series and 59.1% following the booster dose, highlighting the contribution of the booster. However, protection is influenced by antigenic variability among circulating strains, resulting in incomplete and geographically variable coverage. In addition, antibody waning over time and the limited impact on nasopharyngeal carriage reduce the potential for long-term and indirect protection. These factors highlight the need to optimize vaccination strategies, including the timing of booster doses, particularly in adolescents, and the role of vaccination in different epidemiological contexts. In this regard, it is not precisely defined whether infants who were immunized in the first year of life need a booster dose in the preschool period, especially in countries with a high incidence of MenB disease. Moreover, it is not established whether and when adolescents who were vaccinated both in infancy and during the preschool period need a booster dose. Economic considerations and variability in national immunization policies further contribute to heterogeneity in vaccine implementation. Emerging evidence suggests possible cross-protection against other meningococcal serogroups and Neisseria gonorrhoeae, although findings remain inconsistent across different risk groups and do not allow us to recommend 4CMenB vaccine beyond MenB IBD prevention. Conclusions: 4CMenB is an effective tool for preventing MenB IMD, although further studies are needed. Future strategies should prioritize age-targeted boosting and enhanced genomic surveillance to maximize impact. Full article

Background: In March 2026, a meningococcal cluster centred on the University of Kent, England, caused two deaths and resulted in over 20 reported cases within the first week, including confirmed and suspected invasive cases. Subsequent UKHSA updates in early April 2026 reported 21 laboratory-confirmed MenB cases (18 linked to the outbreak strain) and two deaths, with the outbreak subsequently spreading to a second Canterbury university, Canterbury Christ Church University, and confirmed as Neisseria meningitidis serogroup B (MenB). Sub-Saharan Africa (SSA) bears a disproportionate global burden of meningococcal disease, yet university settings remain a critically understudied outbreak amplifier. This narrative review extracts epidemiological and policy lessons from the Kent event and applies them to the SSA context. Methods: We conducted a narrative review following the SANRA criteria, searching PubMed, Embase, Scopus, Google Scholar, and African Journals Online (2000–2026), with supplementary grey literature retrieved from World Health Organisation (WHO), Africa Centre for Disease Control, and United Kingdom Health Security Agency (UKHSA). Outbreak data were drawn from official UKHSA public-health statements (grey literature, archived), the University of Kent communications, and peer-reviewed expert commentary. Results: The Canterbury outbreak exposed six reproducible vulnerabilities: unprotected serogroup circulation (confirmed MenB, not covered for the current university-age cohort), nightlife-linked transmission amplification, delayed serogroup identification, poor student symptom-recognition, inadequate institutional response capacity, and, critically, multi-institutional spread via shared nightlife venues (confirmed extension to Canterbury Christ Church University within five days). Each vulnerability is demonstrably more severe in SSA universities, which face a broader multi-serogroup threat environment (NmA, B, C, W, X), virtually no university-entry vaccination requirement, and critical evidence gap of campus-specific meningococcal evidence in the published literature. Conclusions: This review proposes a five-pillar preparedness framework for SSA tertiary institutions, derived from a synthesis of the Kent outbreak and broader epidemiological evidence, intended to inform policy discussion and future research. Moreover, these should be embedded within a broader age-linked prevention strategy that begins before university entry, particularly during the transition into secondary school in high-risk settings. Priority measures include meningococcal vaccination at key educational transition points, prophylactic antibiotic pre-positioning, serogroup-capable surveillance, symptom-recognition training, and pan-continental alert A predominantly reactive response may carry substantial risk in SSA settings. Full article

Asymptomatic pharyngeal Neisseria meningitidis (Nm) carriage is seen in >30% of sexually transmitted infection (STI) clinic attendees. With increasing reports of Nm urethritis and STI-related invasive disease outbreaks, longitudinal assessment and genomic characterization of Nm among patients at an urban STI clinic population in Columbus, Ohio, was undertaken. This study determined the genomic basis of oropharyngeal, urogenital and rectal Nm isolates carried by patients presenting for care. Cultures using media selective for Neisseria spp., Nm-specific PCR screening of colonies with oxidase-positive Gram-negative diplococci, PCR-based genogrouping and whole-genome sequencing of confirmed Nm were performed. Overall, genomic data of 453 oropharyngeal, 10 urethral, 5 rectal and 1 cervical Nm isolate were obtained between January 2018 and December 2019. Among oropharyngeal Nm isolates, genogrouping identified 37.7% as cnl (capsule null locus), 28% B, 13.5% E, 10.8% Z, 2.6% C and 2.6% Y. However, the cps locus was inactivated in ≥80% of isolates with specified genogroups. The major clonal complexes (ccs) were cc53, cc32, cc41/44, cc1157, cc198 and cc4821. Two oropharyngeal, one rectal and three urethral isolates belonged to the ST-11 Nm urethritis clade (NmUC). Group Y ST-1466 Nm, recently linked to global urogenital and systemic infections, was also identified in the oropharynx. Full article

Background/Objectives: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy caused by dysregulation of the alternative complement pathway, often related to genetic mutations or autoantibodies. The introduction of complement C5 inhibitors, such as eculizumab and ravulizumab, has significantly improved renal and overall outcomes. However, complement inhibition impairs host defense against encapsulated bacteria, markedly increasing the risk of invasive infections, particularly Neisseria meningitidis. Vaccination against meningococcal groups ACWY and B, along with temporary antibiotic prophylaxis, is therefore recommended before initiating anti-C5 therapy. Methods: We report the clinical course of a 13-year-old boy with aHUS secondary to anti–complement factor H (CFH) autoantibodies and CFHR3–CFHR1 homozygous deletion, treated with C5 inhibitors. Results: Despite complete meningococcal vaccination and a previous course of antibiotic prophylaxis, the patient developed meningitis during ongoing complement inhibitor therapy. Conclusions: This case highlights that breakthrough invasive infections may occur despite adherence to recommended preventive strategies. It underscores the need for sustained clinical vigilance, timely vaccine boosters, and careful reassessment of the risk–benefit balance of continued complement inhibition therapy. Full article

Background/Objectives: Bacterial meningitis is a severe disease with a fatality rate of 5–50%. It is mainly caused by Streptococcus pneumoniae or Neisseria meningitidis, which can also cause simultaneous infections outside the central nervous system. Toll-like receptors (TLRs) have an important role in the innate immune system. The TLR2 subfamily comprises the four highly homologous members TLR1, TLR2, TLR6, and TLR10, which also have an important immunomodulatory role in infectious diseases. Methods: The study cohort consists of 190 bacterial meningitis patients aged 1 to 147 months from randomized clinical trials and 268 controls from Luanda, Angola. Polymorphisms of TLR2 (rs111200466) and TLR10 (rs10856837 and rs11096956) were determined using PCR-based methods and Sanger sequencing. The genotyping results were analyzed together with clinical data to determine whether gene polymorphisms of TLR2 and TLR10 are associated with susceptibility and outcome of bacterial meningitis in Angolan children. Results: At admission and during hospitalization, patients with pneumococcal meningitis carrying a variant (ins/del or del/del) of TLR2 rs111200466 had a significantly lower risk of coexisting infections (OR 0.27; 95% CI 0.11–0.65; p = 0.004), particularly pneumonia (OR 0.18; 95% CI 0.06–0.49; p = 0.001). In addition, haplotype analysis demonstrated that a variant genotype of TLR2 rs111200466 together with a wildtype of TLR10 SNPs (rs10856837 and rs11096956) may protect against coexisting pneumonia (OR 0.2; 95% CI 0.06–0.6; p = 0.007). Conclusions: This study suggests an association between coexisting infection and genetic variation in TLR2 and TLR10 of bacterial meningitis in Angolan children. Full article

Background: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis remains a major public health concern due to its severity, lethality, and long-term sequelae. To address the rise in serogroups W and Y in Spain, the Community of Madrid implemented a catch-up campaign in 2019–2021, targeting adolescents (ages 13–18) alongside routine tetravalent meningococcus vaccine (MenACWY) at age 12. This study evaluated MenACWY catch-up vaccination uptake in routine practice by describing vaccine coverage, temporal trends, and associated factors in adolescents born between 2001 and 2006. Methods: A population-based cross-sectional study was conducted using data from the Community of Madrid’s vaccination registry (SISPAL Vacunas). Vaccination coverage was calculated for adolescents with at least one recorded MenACWY dose from age 10 onwards. Temporal trends were analyzed by birth cohort and calendar time, and multivariable logistic regression models were used to identify factors associated with vaccination uptake. Results: Among 424,059 adolescents, overall vaccination coverage by December 2021 was 63.8%, ranging from 54.4% to 78.2% across birth cohorts. Coverage was highest in the 2006 cohort, likely due to co-administration with the tetanus and diphtheria (Td) booster. A slightly higher uptake was observed among females and adolescents with chronic conditions, while foreign-born adolescents consistently showed lower coverage. COVID-19 disruptions led to temporal variability, with sharp declines during lockdowns and partial recoveries thereafter, with persistent sociodemographic differences in uptake. Conclusions: By December 2021, coverage was incomplete, with marked variability across birth cohorts. Higher uptake was observed when vaccination was integrated into routine visits, while persistent sociodemographic disparities remained evident. These observational findings are consistent with the programmatic value of combined catch-up and routine strategies and the need for targeted actions to ensure equitable MenACWY coverage. Full article

Among many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe³⁺ in vertebrate blood. Neisseria meningitidis, a Gram-negative pathogen causing meningitis, relies on iron for survival and acquires it from human transferrin (hTf) using two surface proteins, TbpA and TbpB. These proteins interact with hTf to form a ternary TbpA–TbpB–hTf complex, enabling iron capture from the host. The absence of an experimental crystal structure for this complex has hindered computational studies, a detailed understanding of Fe³⁺ dissociation, and designing efficient therapeutics. This study presents the first computational model of the ternary complex, its validation, and molecular dynamics simulations. Structural analyses revealed key electrostatic interactions regulating Fe³⁺ coordination and essential contact regions between proteins. The role of Lys359 from TbpA was investigated via QM/MM calculations by evaluating Fe³⁺ binding energies of isolated hTf, the ternary complex, and Lys359Ala, Lys359Arg, Lys359Asp mutant models. Results revealed that the proton transfer from Lys359 leads to disruption of Tyr517–Fe³⁺ coordination, facilitating iron transfer to the bacterial system. Natural bond orbital analysis confirmed this mechanism. The findings provide new molecular insight into N. meningitidis iron acquisition and identify Lys359 as a potential target for covalent inhibitor design, guiding the development of novel therapeutics against meningococcal infection. Full article

Cell surface sialylation is utilized by a number of pathogenic bacteria to evade the host immune system through molecular mimicry of host sialoglycoconjugates. Human pathogen Neisseria meningitidis serotype B (NmB) expresses both sialylated capsule and surface lipooligosaccharides as pivotal virulence factors. An essential enzyme in the sialylation pathway of NmB is CMP-sialic acid synthetase (CSS), which produces the activated nucleotide sugar necessary for sialic acid transfer. In this work, novel C-4, -5, -7, and -9 functionalized derivatives of neuraminic acid β-methyl glycoside (Neuβ2Me) were synthesized as candidate CSS inhibitors. A number of these were found to reduce the activity of NmB CSS in vitro. The highest inhibition of NmB CSS, in a mixed mode manner, was observed with a Neu5Acβ2Me C-9 serine carboxamide. Direct interaction with the enzyme was confirmed by Saturation Transfer Difference (STD) NMR. Supplementation of growth media with this compound reduced lipooligosaccharide (LOS) sialylation of living N. meningitidis, thus providing an interesting starting point for the development of specific NmB CSS inhibitors as an alternative treatment strategy to fight bacterial infections. Full article

Introduction: Despite the advances in its prevention, invasive meningococcal disease (IMD) remains a serious health problem worldwide due to its high morbidity and mortality, including in Romania, with 22% mortality rate. The objectives were to describe the trends of IMD cases admitted to a tertiary care hospital in Romania, over 24 years, and the case fatality rate (CFR) by age, year of admission, and Neisseria meningitidis serogroups. Materials and Methods: A retrospective study was conducted in IMD patients admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania, between 2001 and 2024. Results: A total of 256 IMD patients were admitted, 171 under fourteen years, out of which 75 were infants. Most cases were reported before 2008. The case distribution showed 90 patients (35%) with meningitis, 84 (32%) with meningococcaemia, and 82 (32%) with an association of both. Serogroup B was the most frequently and steadily found (58 cases). The overall CFR was 12%. CFR was highest in infants younger than 6 months (19%) and meningococcaemia cases (29%). Conclusions: In our study, IDM had the highest frequency and CFR in infants and meningococcaemia cases. The trends showed a decline in cases after 2008. Serogroup B was the most prevalent and stable strain over 24 years. Full article

Background: During the COVID-19 pandemic, reductions in cases of bacterial diseases transmitted via the respiratory route were reported by the Invasive Respiratory Infection Surveillance Consortium. Here, we evaluate the epidemiology of invasive meningococcal disease (IMD) in Argentina, Brazil, Chile, and Colombia during and after the COVID-19 pandemic. Methods: The epidemiology of meningococcal disease was reviewed in selected South American countries through 2023 from publicly available national surveillance system databases. Results: The incidence of IMD decreased substantially in 2020 in Argentina, Brazil, Chile, and Colombia and was followed by a trend of increased disease. Similarly to observations in several European countries, the post-pandemic rebounds in cases of IMD in the four South American countries included in this analysis were mainly caused by serogroup B, that became one of the predominant serogroups causing IMD in all four countries. Conclusions: Enhanced surveillance of IMD, including genomic characterization of strains, is needed to inform public health policymakers and guide future vaccination strategies in the region. Full article

Background: The 4CMenB vaccine (Bexsero^®) contains surface proteins from Neisseria meningitidis serogroup B and is recommended from 2 months of age. The most frequently reported adverse events are fever, injection site pain, and fatigue. Thus, this study aimed to estimate the incidence of local and systemic adverse events associated with the administration of the 4CMenB (Bexsero^®) vaccine. Methods: A systematic review and meta-analysis of clinical trials published up to 28 February 2025 were conducted using PubMed, ScienceDirect, and Web of Science. Human studies available in English, Spanish, French, German, or Italian were exclusively included. Adverse events following the first dose of the vaccine were analyzed. Pooled proportions with 95% confidence intervals were calculated, and heterogeneity across studies was assessed using the I² statistics. Results: Ten clinical trials comprising 13,345 participants were included. The most common adverse event was local pain (occurring in up to 94% of cases), followed by induration, erythema, and edema, with frequencies ranging from 25% to 45%. The most frequently reported systemic events were irritability (up to 75%), fatigue (51–59%), fever (up to 60%), headache (42–49%), and persistent crying (50–65%). Most adverse events were mild and self-limiting. Conclusions: The 4CMenB (Bexsero) vaccine exhibits a favorable safety profile, characterized by a predominance of mild and transient local adverse events. Although several systemic events were reported, their overall frequency was generally low. These findings support the continued inclusion of Bexsero^® in routine childhood immunization programs. Full article

Background/Objectives: This study aimed to evaluate the immunogenicity and safety of a Meningococcal A and C Polysaccharide Conjugate Vaccine in 3–5-month-old infants. A single-center, randomized, blinded, positive-controlled phase III clinical trial was conducted in Binyang County, Guangxi Zhuang Autonomous Region, China. Infants aged 3–5 months were randomly assigned to the experimental or control group at a 1:1 ratio. Both groups received 3 primary doses with a 1-month interval between each dose, and a booster dose administered at 18 months of age. Seroconversion rate, seropositivity rate, and GMT of bactericidal antibodies against Neisseria meningitidis groups A and C were assessed, along with adverse reactions within the full course of primary immunization and 30 days after booster immunization. Results: After primary immunization, in the experimental group’s pre-vaccination antibody-negative infants, seroconversion rates for groups A and C exceeded 90%, with antibody fold increases over 90 times; its seroconversion rates and GMT were non-inferior to the control group. Before the 18-month booster, the experimental group’s group A and C antibody seropositivity rates dropped to approximately 70% and 30% (slightly higher than the control), respectively. After booster immunization, the antibody levels against groups A and C were significantly higher than those before the booster and the positive rates and GMT levels of the two groups were similar. Adverse reactions were mainly solicited systemic ones (fever most common), with no statistical difference between groups. Conclusions: The experimental vaccine shows great immunogenicity and safety in infants aged 3–5 months and is non-inferior to the control vaccine. In the booster immunization phase of the control group, sequential vaccination with vaccines from different manufacturers was adopted, and the immunogenicity was good. Full article

The increase in the incidence and antibiotic-resistant strains show a need for a broadly protective vaccine to prevent gonorrhea. OMVax has developed a combination vaccine based on native outer membrane vesicles (NOMVs) from two Neisseria meningitidis (Nm) and two Neisseria gonorrhoeae (Ng) strains. The strains had the acyl transferase LpxL1 knocked out to increase safety, and the reduction-modifiable protein was also knocked out in the Ng strains. Factor H binding protein (FHbp) mutants with reduced Factor H (FH) binding from Subfamilies A and B, respectively, were overexpressed in the Nm strains. The Ng strains individually expressed porin outer membrane protein B 1a (PorB.1a) or PorB.1b. Antibodies elicited by the Nm-Ng NOMV vaccine had SBA with a human complement against diverse Nm and Ng strains grown in the presence of Cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-NANA), had no significant reduction in serum bactericidal activity (SBA) compared to the respective individual vaccines, inhibited the adhesion to human cervical and vaginal cells in five out of six Ng strains tested, and inhibited Nm and Ng colonization in a transgenic mouse model. In conclusion, the Nm-Ng NOMV vaccine has the potential to protect against disease and inhibit colonization by diverse Nm and Ng strains, which may be an advantage for controlling the disease through vaccination, particularly in the adolescent/young adult age group. Full article