Meningococcal Research Articles

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

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

Predictive signs and symptoms of bacterial meningitis isolates in Northern Ghana

Cerebrospinal meningitis (CSM) is a public health burden in Ghana that causes up to 10% mortality in confirmed cases annually. About 20% of those who survive the infection suffer permanent sequelae. The study sought to understand the predictive signs and symptoms of bacterial meningitis implicated in its outcomes. Retrospective data from the Public Health Division, Ghana Health Service on bacterial meningitis from 2015 to 2019 was used for this study. A pre-tested data extraction form was used to collect patients’ information from case-based forms kept at the Disease Control Unit from 2015 to 2019. Data were transcribed from the case-based forms into a pre-designed Microsoft Excel template. The data was cleaned and imported into SPSS version 26 for analysis. Between 2015 and 2019, a total of 2446 suspected bacterial meningitis cases were included in the study. Out of these, 842 (34.4%) were confirmed. Among the confirmed cases, males constituted majority with 55.3% of the cases. Children below 14 years of age were most affected (51.4%). The pathogens commonly responsible for bacterial meningitis were Neisseria meningitidis (43.7%) and Streptococcus pneumoniae (53.0%) with their respective strains Nm W135 (36.7%), Nm X (5.1%), Spn St. 1 (26.2%), and Spn St. 12F/12A/12B/44/4 (5.3%) accounting for more than 70.0% of the confirmed cases. The presence of neck stiffness (AOR = 1.244; C.I 1.026–1.508), convulsion (AOR = 1.338; C.I 1.083–1.652), altered consciousness (AOR = 1.516; C.I 1.225–1.876), and abdominal pains (AOR = 1.404; C.I 1.011–1.949) or any of these signs and symptoms poses a higher risk for testing positive for bacterial meningitis adjusting for age. Patients presenting one and/or more of these signs and symptoms (neck stiffness, convulsion, altered consciousness, and abdominal pain) have a higher risk of testing positive for bacterial meningitis after statistically adjusting for age.

Inhibitory mechanism of CRISPR-Cas9 by AcrIIC4.

CRISPR-Cas systems act as the adaptive immune systems of bacteria and archaea, targeting and destroying invading foreign mobile genetic elements (MGEs) such as phages. MGEs have also evolved anti-CRISPR (Acr) proteins to inactivate the CRISPR-Cas systems. Recently, AcrIIC4, identified from Haemophilus parainfluenzae phage, has been reported to inhibit the endonuclease activity of Cas9 from Neisseria meningitidis (NmeCas9), but the inhibition mechanism is not clear. Here, we biochemically and structurally investigated the anti-CRISPR activity of AcrIIC4. AcrIIC4 folds into a helix bundle composed of three helices, which associates with the REC lobe of NmeCas9 and sgRNA. The REC2 domain of NmeCas9 is locked by AcrIIC4, perturbing the conformational dynamics required for the target DNA binding and cleavage. Furthermore, mutation of the key residues in the AcrIIC4-NmeCas9 and AcrIIC4-sgRNA interfaces largely abolishes the inhibitory effects of AcrIIC4. Our study offers new insights into the mechanism of AcrIIC4-mediated suppression of NmeCas9 and provides guidelines for the design of regulatory tools for Cas9-based gene editing applications.

Immune responses to Neisseria gonorrhoeae and implications for vaccine development.

Neisseria gonorrheoae is the causative agent of gonorrhea, a sexually transmitted infection responsible for a major burden of disease with a high global prevalence. Protective immunity to infection is often not observed in humans, possible due to high variability of key antigens, induction of blocking antibodies, or a large number of infections being relatively superficial and not inducing a strong immune response. N. gonorrhoeae is a strictly human pathogen, however, studies using mouse models provide useful insights into the immune response to gonorrhea. In mice, N. gonorrhoea appears to avoid a protective Th1 response by inducing a less protective Th17 response. In mouse models, candidate vaccines which provoke a Th1 response can accelerate the clearance of gonococcus from the mouse female genital tract. Human studies indicate that natural infection often induces a limited immune response, with modest antibody responses, which may correlate with the clinical severity of gonococcal disease. Studies of cytokine responses to gonococcal infection in humans provide conflicting evidence as to whether infection induces an IL-17 response. However, there is evidence for limited induction of protective immunity from a study of female sex workers in Kenya. A controlled human infection model (CHIM) has been used to examine the immune response to gonococcal infection in male volunteers, but has not to date demonstrated protection against re-infection. Correlates of protection for gonorrhea are lacking, which has hampered the progress towards developing a successful vaccine. However, the finding that the Neisseria meningitidis serogroup B vaccines, elicit cross-protection against gonorrhea has invigorated the gonococcal vaccine field. More studies of infection in humans, either natural infection or CHIM studies, are needed to understand better gonococcal protective immunity.

Epidemiological Differences in Hajj-Acquired Airborne Infections in Pilgrims Arriving from Low and Middle-Income versus High-Income Countries: A Systematised Review.

This systematised review aims to compare the epidemiological patterns of Hajj-acquired airborne infections among pilgrims from low and middle-income countries (LMIC) versus those from high-income countries (HIC). A PubMed search was carried out for all published articles before February 2023, using a combination of MeSH terms and text words. The Newcastle-Ottawa Scale (NOS) was used to assess data quality. From a total of 453 titles identified, 58 studies were included in the review (LMIC = 32, and HIC = 26). In the pooled sample, there were 27,799 pilgrims aged 2 days to 105 years (male: female = 1.3:1) from LMIC and 70,865 pilgrims aged 2 months to 95 years (male: female = 1:1) from HIC. Pilgrims from both HIC and LMIC had viral and bacterial infections, but pilgrims from HIC tended to have higher attack rates of viral infections than their LMIC counterparts. However, the attack rates of bacterial infections were variable: for instance, pilgrims from LMIC seemed to have higher rates of meningococcal infections (0.015-82% in LMIC vs. 0.002-40% in HIC) based on the study population, but not Mycobacterium tuberculosis (0.7-20.3% in LMIC vs. 38% in HIC). Targeted measures are needed to prevent the spread of airborne infections at Hajj.

Mathematical model for the dynamics of bacterial meningitis (Meningococcal meningitis): a case study of Yobe State Specialist Hospital, Damaturu, Nigeria

A model for bacterial meningitis was created by adding a class of transporters to the basic Susceptible Carrier Infected and Recovered (SCIR) model, since vaccination and treatment are the best methods of controlling the transmission of most overpowering sicknesses. Immunization assists helpless people with building either a drawn out invulnerability or transient resistance while treatment decreases the quantity of sickness actuated passing and the quantity of irresistible people locally or country. This study comprises of a mathematical model for bacterial meningitis dynamics that can be used to a wide range of mathematical modeling problems. In this exploration, a nonlinear deterministic model with time reliance controls has been proposed to depict the elements of bacterial meningitis in a populace. We discovered that the (EEP) and (DFE) are locally asymptotically stable in our study. We now advise the researcher to determine whether it is globally asymptotically stable in order to achieve optimal disease control. The presence of an endemic harmony and the calculation of the reproduction number . The mathematical arrangement shows that vaccinating vulnerable people will prompt disposal of the infection in the public and furthermore it will lessen the weight on wellbeing suppliers. Numerical simulations were presented to explain the parameters in the end path in the model were carried out by using MAPLE software. Most likeable of this research work shows that the rate at which treatment and vaccination rate increases to the higher value the recovered compartment increases to the peak point. This means treatment and vaccination has an impact on reducing the case of bacterial meningitis in a population. Now we conclude that a high infection transmission rate requires a high vaccine and treatment rate on the effect of vaccination against meningitis.

Nasopharyngeal Meningococcal Carriage among Older Adults in Türkiye (MeninGOLD Study).

Introduction: While there is a significant amount of information about invasive meningococcal disease (IMD), meningococcal carriage, and meningococcal vaccines in children and adolescents, data in older adults are limited. Studies of meningococcal carriage and transmission modeling can be utilized to predict the spread of IMD and guide prevention and treatment strategies. Our study's main objective was to assess the prevalece of Neisseria meningitidis (Nm) carriage, serogroup distribution, and associated risk factors among older adults in Türkiye. Methods: Nasopharyngeal samples were collected between December 2022 and January 2023 from a total of 329 older adults (65 years of age and above). The samples were tested via PCR for Nm, and a serogroup (A, B, C, Y, W, X, E, Z, H) analysis of the positive samples was performed. Results: In total, 329 adults over 65 years of age (150 females and 179 males; 69% were 65-75 years old and 31% were 75 years of age and older) were included in the study. Nm carriage was detected in 46 participants (13.9%), and the serogroup distribution was as follows: 2.4% MenY (n = 8), 1.8% MenB (n = 6), 0.2% MenW (n = 2), and 9.4% non-groupable (n = 31). Other serogroups were not detected. Between the meningococcal carriers and the non-carriers, there were no differences between previous vaccination histories (meningococcal, pneumococcal, influenza, and COVID-19), travel history for Hajj and/or Umrah, and the presence of chronic disease. Of the 16 cases positive for the serogroups Y, B, and W, 13 patients were between the ages of 65 and 74 and three patients were over 75 years old, and these three cases represented MenY. Conclusion: In our study, the percentage of meningococcal carriage was found to be 13.9%, the carriage rate for encapsulated strains was 4.8%, and the most common serogroup was MenY. Men Y was also the only serogroup detected in patients over 75 years of age. The MenY serogroup, which is one of the most important causes of IMD (especially in pneumonia cases) in people older than 65 years, was the most frequently carried serogroup in people over 65 years of age in our study. Adequate surveillance and/or a proper carriage study would help to define potential vaccination strategies for older adults.

Evaluation of Laboratories Supporting Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance in the World Health Organization African Region, through the Performance of Coordinated External Quality Assessment.

(1) Background: Laboratories supporting the invasive bacteria preventable disease (IB-VPD) network are expected to demonstrate the capacity to identify the main etiological agents of pediatric bacterial meningitis (PBM) (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) on Gram stains and in phenotypic identification. Individual reports of sentinel site (SSL), national (NL) and regional reference (RRL) laboratories participating in the World Health Organization (WHO)-coordinated external quality assessment, distributed by the United Kingdom National External Quality Assessment (EQA) Services (UK NEQAS) for Microbiology between 2014 and 2019 were analyzed. (2) Methods: The panels consisted of (1) unstained bacterial smears for Gram staining, (2) viable isolates for identification and serotyping/serogrouping (ST/SG) and (3) simulated cerebral spinal fluid (CSF) samples for species detection and ST/SG using polymerase chain reaction (PCR). SSLs and NLs tested for Gram staining and species identification (partial panel). RRLs, plus any SSLs and NLs (optionally) also analyzed the simulated CSF samples (full panel). The passing score was ≥75% for NLs and SSLs, and ≥90% for RRLs and NLs/SSLs testing the full panel. (3) Results: Overall, 63% (5/8) of the SSLs and NLs were able to correctly identify the targeted pathogens, in 2019; but there were challenges to identify Haemophilus influenzae either on Gram stains (35% of the labs failed 2014), or in culture. Individual performance showed inconsistent capacity, with only 39% (13/33) of the SSLs/NLs passing the EQA exercise throughout all surveys in which they participated. RRLs performed well over the study period, but one of the two failed to reach the minimal passing score in 2016 and 2018; while the SSLs/NLs that optionally tested the full panel scored between 75% and 90% (intermediate pass category). (4) Conclusions: We identified a need for implementing a robust quality management system for timely identification of the gaps and then implementing corrective and preventive actions, in addition to continuous refresher training in the SSLs and NLs supporting the IB-VPD surveillance in the World Health Organization, Regional Office for Africa (WHO AFRO).

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial

Immunogenicity and safety of a pentavalent meningococcal ABCWY vaccine in adolescents and young adults: an observer-blind, active-controlled, randomised trial

A new era for equity in meningococcal disease prevention

A new era for equity in meningococcal disease prevention

Pangenome graphs in infectious disease: a comprehensive genetic variation analysis of Neisseria meningitidis leveraging Oxford Nanopore long reads.

Whole genome sequencing has revolutionized infectious disease surveillance for tracking and monitoring the spread and evolution of pathogens. However, using a linear reference genome for genomic analyses may introduce biases, especially when studies are conducted on highly variable bacterial genomes of the same species. Pangenome graphs provide an efficient model for representing and analyzing multiple genomes and their variants as a graph structure that includes all types of variations. In this study, we present a practical bioinformatics pipeline that employs the PanGenome Graph Builder and the Variation Graph toolkit to build pangenomes from assembled genomes, align whole genome sequencing data and call variants against a graph reference. The pangenome graph enables the identification of structural variants, rearrangements, and small variants (e.g., single nucleotide polymorphisms and insertions/deletions) simultaneously. We demonstrate that using a pangenome graph, instead of a single linear reference genome, improves mapping rates and variant calling for both simulated and real datasets of the pathogen Neisseria meningitidis. Overall, pangenome graphs offer a promising approach for comparative genomics and comprehensive genetic variation analysis in infectious disease. Moreover, this innovative pipeline, leveraging pangenome graphs, can bridge variant analysis, genome assembly, population genetics, and evolutionary biology, expanding the reach of genomic understanding and applications.

A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.

Meningococcal factor H-binding protein: implications for disease susceptibility, virulence, and vaccines.

Neisseria meningitidis is a human-adapted pathogen that causes meningitis and sepsis worldwide. N. meningitidis factor H-binding protein (fHbp) provides a mechanism for immune evasion by binding human complement factor H (CFH) to protect it from complement-mediated killing. Here, we discuss features of fHbp which enable it to engage human CFH (hCFH), and the regulation of fHbp expression. Studies of host susceptibility and bacterial genome-wide association studies (GWAS) highlight the importance of the interaction between fHbp and CFH and other complement factors, such as CFHR3, on the development of invasive meningococcal disease (IMD). Understanding the basis of fHbp:CFH interactions has also informed the design of next-generation vaccines as fHbp is a protective antigen. Structure-informed refinement of fHbp vaccines will help to combat the threat posed by the meningococcus, and accelerate the elimination of IMD.

Disease profiles in the Indigenous Australian population are suggestive of a common complement control haplotype.

Aboriginal and Torres Strait Islander People (respectfully referred to as Indigenous Australians herein) are disparately burdened by many infectious and chronic diseases relative to Australians with European genetic ancestry. Some of these diseases are described in other populations to be influenced by the inherited profile of complement genes. These include complement factor B, H, I and complement factor H-related (CFHR) genes that can contribute to a polygenic complotype. Here the focus is on the combined deletion of CFHR1 and 3 to form a common haplotype (CFHR3-1Δ). The prevalence of CFHR3-1Δ is high in people with Nigerian and African American genetic ancestry and correlates to a higher frequency and severity of systemic lupus erythematosus (SLE) but a lower prevalence of age-related macular degeneration (AMD) and IgA-nephropathy (IgAN). This pattern of disease is similarly observed among Indigenous Australian communities. Additionally, the CFHR3-1Δ complotype is also associated with increased susceptibility to infection with pathogens, such as Neisseria meningitidis and Streptococcus pyogenes, which also have high incidences in Indigenous Australian communities. The prevalence of these diseases, while likely influenced by social, political, environmental and biological factors, including variants in other components of the complement system, may also be suggestive of the CFHR3-1Δ haplotype in Indigenous Australians. These data highlight a need to define the Indigenous Australian complotypes, which may lead to the discovery of new risk factors for common diseases and progress towards precision medicines for treating complement-associated diseases in Indigenous and non-Indigenous populations. Herein, the disease profiles suggestive of a common complement CFHR3-1Δ control haplotype are examined.

MAGLIO study: epideMiological Analysis on invasive meninGococcaL disease in Italy: fOcus on hospitalization from 2015 to 2019.

This study analyzed hospital admissions for invasive meningococcal disease (IMD) in epidemiological and economic terms in Italy from 2015 to 2019. The volume of acute admissions for meningococcal diagnosis was analyzed in the period from 2015 to 2019. IMD admissions were identified by ICD-9-CM diagnoses. Costs were assessed using current DRG tariffs. In 2019, a total of 237 admissions for meningococcal disease were recorded in Italy. The mean age of patients was 36.1years. Lumbar puncture was reported in only 14% of hospital discharge forms. From 2015 to 2019, there was a mean annual reduction of - 1.2% nationally for IMD hospitalizations. For 2019, the total costs for acute inpatient admissions were €2,001,093. Considering annual incidence due to IMD, a significant decrease was noted in the age group from 0 to 1year (p = 0.010) during 2015-2019. For all years, mortality associated with meningeal syndrome was lower compared to septic shock with or without meningitis. From 2015 to 2019, hospitalizations for IMD appear to be decreasing slightly in Italy, even if mortality remains high. Favorable trends in hospitalizations for IMD were seen in the 0-1-year age group, which may be attributable to increased vaccination. Costs of hospitalizations for IMD remain high.

Stability of lyophilized Meningococcal A conjugate vaccine, (MenAfriVac™) at elevated temperatures to support controlled temperature chain (CTC) claim

Meningococcal A Conjugate Vaccine (MenAfriVac) is the world’s first Monovalent Conjugate Vaccine against Neisseria Meningitidis serogroup A which has obtained Controlled Temperature Chain (CTC) label claim of “stable upto 40°C for 4 days prior to reconstitution” developed by Serum Institute of India Pvt. Ltd. Pune, India and the vaccine was granted permission from World health Organization. This paper elucidates and talks about the layout of various studies performed to characterize the product to declare as CTC at the time when the knowledge and mechanism to describe CTC was not fully known which in term helped to design the CTC guidelines.Product stability was assessed using clinical, consistency and regular lots released by NRA. The critical stability indicating parameters like free polysaccharide, molecular size distribution along with Potency and safety tests were carried out to support the product stability making sure it also qualifies for Vaccine Vial Monitor label claim of VVM30. An additional in use stability (reconstitution) was also performed. All studies indicated that the product remains stable at real time as well as elevated temperatures and well within the specifications approved by NRA and formed the strong basis for CTC claim which is now recommended by WHO.

Computer Aided Reverse Vaccinology: A Game-changer Approach for Vaccine Development.

One of the most dynamic approaches in biotechnology is reverse vaccinology, which plays a huge role in today's developing vaccines. It has the capability of exploring and identifying the most potent vaccine candidate in a limited period of time. The first successful novel approach of reverse vaccinology was observed in Neisseria meningitidis serogroup B, which has revolutionised the whole field of computational biology. In this review, we have summarized the application of reverse vaccinology for different infectious diseases, discussed epitope prediction and various available bioinformatic tools, and explored the advantages, limitations and necessary elements of this approach. Some of the modifications in the reverse vaccinology approach, like pan-genome and comparative reverse vaccinology, are also outlined. Vaccines for illnesses like AIDS and hepatitis C have not yet been developed. Computer Aided Reverse vaccinology has the potential to be a game-changer in this area. The use of computational tools, pipelines and advanced soft-computing methods, such as artificial intelligence and deep learning, and exploitation of available omics data in integration have paved the way for speedy and effective vaccine designing. Is reverse vaccinology a viable option for developing vaccines against such infections, or is it a myth? Vaccine development gained momentum after the spread of various infections, resulting in numerous deaths; these vaccines are developed using the traditional technique, which includes inactivated microorganisms. As a result, reverse vaccinology may be a far superior technique for creating an effective vaccine.

Meningococcal burden of disease in Argentina: 10 years epidemiologic review

ABSTRACT Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition, mainly affecting infants. In 2017, Argentina introduced a vaccination program against serogroups A, C, W and Y (MenACWY) for infants aged 3, 5 and 15 months and adolescents aged 11 years. The objective of this study was to review the burden of IMD in Argentina in 2010–2019. Data were obtained from national surveillance databases, and the study estimated IMD incidence, mortality, case-fatality rates, and serogroup distributions across age groups. A total of 1,972 IMD cases were reported in the study period, with the highest incidence in infants aged < 1 year. Incidence peaked in 2013 and subsequently declined. Mortality rates were 18 times higher in infants than in other age groups, reflecting the high impact of IMD in this age group. The case-fatality rate was 8.5% on average and increased with age. The proportion of notified cases with serogroup identification increased over the period, reaching 91% in 2019. The most common serogroups over the study period were serogroup B (48%) and serogroup W (42%), with an increase in B relative to W since 2015. In infants aged < 1 year, the proportion of serogroup B increased in recent years, reaching around 70% of characterized cases in 2018–2019. These results show the dynamism of IMD and indicate the importance of vaccination at an early age and offering protection against predominant serogroups. These data are valuable to support evidence-based decision-making in healthcare.

Comparative Transcriptome Profiling of mRNA and lncRNA of Mouse Spleens Inoculated with the Group ACYW135 Meningococcal Polysaccharide Vaccine.

The Group ACYW135 meningococcal polysaccharide vaccine (MPV-ACYW135) is a classical common vaccine used to prevent Neisseria meningitidis serogroups A, C, Y, and W135, but studies on the vaccine at the transcriptional level are still limited. In the present study, mRNAs and lncRNAs related to immunity were screened from the spleens of mice inoculated with MPV-ACYW135 and compared with the control group to identify differentially expressed mRNAs and lncRNAs in the immune response. The result revealed 34375 lncRNAs and 41321 mRNAs, including 405 differentially expressed (DE) lncRNAs and 52 DE mRNAs between the MPV group and the control group. Results of GO and KEGG enrichment analysis turned out that the main pathways related to the immunity of target genes of those DE mRNAs and DE lncRNAs were largely associated with positive regulation of T cell activation, CD8-positive immunoglobulin production in mucosal tissue, alpha-beta T cell proliferation, negative regulation of CD4-positive, and negative regulation of interleukin-17 production, suggesting that the antigens of MPV-ACYW135 capsular polysaccharide might activate T cell related immune reaction in the vaccine inoculation. In addition, it was noted that Bach2 (BTB and CNC homolog 2), the target gene of lncRNA MSTRG.17645, was involved in the regulation of immune response in MPV-ACYW135 vaccination. This study provided a preliminary catalog of both mRNAs and lncRNAs associated with the proliferation and differentiation of body immune cells, which was worthy of further research to enhance the understanding of the biological immune process regulated by MPV-ACYW135.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium

The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.