Search

Objective: Serogroup W and Y invasive meningococcal disease increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) invasive meningococcal disease, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, the vaccine coverage in the eligible school cohorts aged 14 to 19 years was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage., Methods: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15 to 19 years, using two cross-sectional studies: 2014 to 2015 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406)., Results: A total of 10 625 participants preimplementation and 13 438 postimplementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2.03 to 0.71% (OR 0.34 [95% CI 0.27-0.44], p < 0.001). Carriage of genogroup B meningococci did not change (1.26% vs 1.23% [95% CI 0.77-1.22], p = 0.80) and genogroup C remained rare (n = 7/10 625 vs 17/13 438, p = 0.135). The proportion of serogroup positive isolates (i.e. those expressing capsule) decreased for genogroup W by 53.8% (95% CI -5.0 - 79.8, p = 0.016) and for genogroup Y by 30.1% (95% CI 8.946·3, p = 0.0025)., Discussion: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Neisseria meningitidis is an obligate human commensal bacterium that frequently colonises the upper respiratory tract. Person-to-person transmission occurs via direct contact or through dispersion of respiratory droplets from a carrier of the bacteria, and can lead to invasive meningococcal disease. Rare sporadic cases of meningococcal urogenital and anorectal infections, including urethritis, proctitis, and cervicitis, have been reported, typically following orogenital contact with an oropharyngeal meningococcal carrier. The resulting infections were clinically indistinguishable from infections caused by Neisseria gonorrhoeae. Over the past two decades, there have also been multiple outbreaks across North America and Europe of invasive meningococcal disease among men who have sex with men (MSM). The responsible meningococci belong to a highly virulent and predominantly serogroup C lineage, including strains that are able to express nitrite reductase and grow in anaerobic environments, such as the urogenital and anorectal tracts. More recently, a distinct clade within this lineage has expanded to cause urethritis predominantly among men who have sex with women. Evolutionary events giving rise to this clade included the loss of the ability to express a capsule, and acquisition of several gonococcal alleles, including one allele encoding a highly efficient gonococcal nitrite reductase. Members of the clade continue to acquire gonococcal alleles, including one allele associated with decreased antibiotic susceptibility. This evolution has implications for the clinical and public health management of those who are infected and their close contacts, in terms of both antibiotic treatment, and prevention through vaccination., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In September, 2015, the UK became the first country to introduce the multicomponent group B meningococcal (MenB) vaccine (4CMenB, Bexsero) into a publicly funded national immunisation programme. A reduced two-dose priming schedule was offered to infants at 2 months and 4 months, alongside an opportunistic catch-up for 3 month and 4 month olds. 4CMenB was predicted to protect against 73-88% of MenB strains. We aimed to assess the effectiveness and impact of 4CMenB in vaccine-eligible infants in England., Methods: Public Health England (PHE) undertakes enhanced surveillance of meningococcal disease through a combination of clinical, public health, and laboratory reporting. Laboratory-confirmed cases of meningococcal disease are followed up with PHE local health protection teams, general practitioners, and hospital clinicians to collect demographic data, vaccination history, clinical presentation, and outcome. For cases diagnosed between Sept 1, 2015, and June 30, 2016, vaccine effectiveness was assessed using the screening method. Impact was assessed by comparing numbers of cases of MenB in vaccine-eligible children to equivalent cohorts in the previous 4 years and to cases in vaccine-ineligible children., Findings: Coverage of 4CMenB in infants eligible for routine vaccination was high, achieving 95·5% for one dose and 88·6% for two doses by 6 months of age. Two-dose vaccine effectiveness was 82·9% (95% CI 24·1-95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%. Compared with the prevaccine period, there was a 50% incidence rate ratio (IRR) reduction in MenB cases in the vaccine-eligible cohort (37 cases vs average 74 cases; IRR 0·50 [95% CI 0·36-0·71]; p=0·0001), irrespective of the infants' vaccination status or predicted MenB strain coverage. Similar reductions were observed even after adjustment for disease trends in vaccine-eligible and vaccine-ineligible children., Interpretation: The two-dose 4CMenB priming schedule was highly effective in preventing MenB disease in infants. Cases in vaccine-eligible infants halved in the first 10 months of the programme. While ongoing national surveillance will continue to monitor the longer-term impact of the programme, these findings represent a step forward in the battle against meningococcal disease and will help reassure that the vaccine protects against this deadly infection., Funding: Public Health England., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds., Methods: In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850., Findings: Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified., Interpretation: Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented., Funding: Novartis Vaccines., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Background: The religious seasons of Hajj and Umra in the Kingdom of Saudi Arabia (KSA) have historically been associated with epidemics of meningococcal disease. Due to the effective preventive measures taken in recent years, including vaccination, no meningococcal outbreaks have been reported during Hajj or were Hajj-associated. However, little is known about the immunological profile of pilgrims. The aim of this study was to assess the immunological profile of pilgrims on arrival in KSA against the four meningococcal serogroups, A, C, W, and Y, contained within the quadrivalent vaccine., Methods: Following consent, socio-demographic factors and health-related information was collected from pilgrims arriving at King Abdul Aziz International Airport and a blood sample taken. Antibodies were quantified by serum bactericidal antibody assay using baby rabbit complement (rSBA) against the four meningococcal serogroups, A, C, W, and Y., Results: Serum samples were collected from 796 pilgrims; rSBA results were obtained for all four serogroups for 741 of these samples. A total of 48 (6.5%) Hajjis had previously attended Hajj, ranging from 1 to 14 times (median 2 times); 98.2% had received meningococcal quadrivalent vaccine in the last 3 years. Of the 13 who had not, all originated from Bangladesh, with four reporting no previous meningococcal vaccination and nine reporting having received the vaccination more than 3 years ago. For serogroup A, only one pilgrim from Indonesia had an rSBA titre <8. For serogroups C, W, and Y, the percentages of pilgrims with rSBA titres <8 were 9.9%, 17.4%, and 9.4%, respectively. Of note was the high prevalence of non-complement-mediated lysis in pilgrims originating from Nigeria (28/47; 59.6%) and Afghanistan (21/47; 44.7%), but not the other countries. This may be a reflection of the type and pattern of antibiotic usage among these communities., Conclusion: The vast majority of pilgrims are vaccinated and protected against meningococcal serogroups A, C, W, and Y.

Colonization of the nasopharyngeal mucosa by meningococcus and other polysaccharide (PS)-encapsulated bacteria precedes invasion. PS-conjugate vaccines induce PS-specific B-cell memory (B(MEM)) and also prevent colonization, thus blocking person-to-person transmission, generating herd protection. However, in isolation the B(MEM) are unable to sustain immunity. Furthermore, the duration of herd protection the vaccines induce appears limited. We demonstrate that, despite the persistence of PS-specific B(MEM), the population is not maintained within the nasopharynx. Although booster immunization results in the transient appearance of PS-specific B(MEM) within the mucosa, this reflects the re-circulation of systemic B(MEM) through the site rather than the generation of resident mucosal B(MEM). The induction of sustained PS-specific B(MEM) in the nasopharynx would allow the population to be activated by colonization, thus inhibiting subsequent invasion. It would also be expected to boost local mucosal immunity, thus extending herd protection. Strategies to generate PS-specific B(MEM) in the mucosa warrant further investigation.

Objectives: To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients., Methods: A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18 years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria., Results: 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events., Conclusions: Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Neisseria meningitidis is a major cause of both meningitis and septicemia. Typically, isolates are characterized by using a combination of immunological phenotyping, using monoclonal and polyclonal antisera, and Sanger nucleotide sequencing of epitope-encoding variable regions, although these methods can be both time-consuming and limited by reagent availability. Herein, we describe and evaluate a novel microarray to define the porB and porA serotypes of N. meningitidis by the resequencing of variable regions in a single hybridization reaction. PCR products for each gene were amplified, pooled in equimolar concentrations, hybridized to the microarray, and analyzed using Affymetrix GeneChip DNA Analysis Software. Resequencing of the microarray data was then validated by comparison with sequencing data. Molecular profiles were generated for 50 isolates that were combinations of phenotypically typeable (ie, PorA and PorB) and non-typeable (PorB only) isolates. Microarray-generated profiles from isolates with a PorB phenotype were concordant with predicted profiles compared with a previously described typing scheme. In addition, 42% (8 of 19) of previously non-typeable samples were assigned a PorB type when tested using the microarray. The remaining isolates were novel types for which no typing antisera are currently available. The porA data were 97% concordant with Sanger nucleotide sequencing. These results suggest that that microarray resequencing may be a useful tool for the characterization of meningococci, particularly for those isolates that cannot be phenotyped, offering an alternative to conventional sequencing methods.

We investigated the carriage of serogroup W135 meningococci and its relationship with protective immunity in Niamey. Between February and May 2003, three oropharyngeal swabs and two serum samples were each taken from 287 school children. Serogroup W135 isolates were obtained from 8.9% of children. Specific IgG > or = 2 microg/ml using ELISA or serum bactericidal assay (SBA) titre > or = 8 were supposed to represent the protective immunity to a serogroup. The proportion of children with serogroup W135-specific IgG > or = 2 microg/ml increased significantly during follow-up (13.9% to 19.1%), but not the proportion of those with SBA titre > or = 8 (10.1% to 11.6%). At the end of the follow-up, we observed a significant association between carriage of serogroup W135 strains and presumed protective immunity to this serogroup, using either ELISA or SBA. Among 240 children having an initial SBA titre < 8, 20 carried serogroup W135 strains at least once. In May, 25% of carriers had an SBA titre > or = 8, vs. 2.3% of non-carriers. For ELISA, 230 children had specific IgG < 2 microg/ml in February, with 22 having at least one swab positive for serogroup W135 meningococci later. In May, 45.5% of them had specific IgG > or = 2 microg/ml vs. 5.3% among non-carriers.

Serum IgG levels specific for Streptococcus pneumoniae are currently quantified using the ELISA. However, this method has significant limitations in that a separate test is required for each serotype-specific antibody. Here, we describe a rapid and simple method for the simultaneous quantitation of IgG to nine pneumococcal serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F). Pneumococcal polysaccharides were covalently attached to fluorescent microspheres and these beads were serologically assessed using 89-SF standard serum. The multiplex assay was linear over a 24-fold serum dilution range and comparison of monoplex and nonaplex assays revealed no evidence of bead interference. The nonaplex assay was shown to be specific with <30% heterologous inhibition occurring and assay sensitivity was high with the LOD ranging between 32.3 and 109.7 pg/ml. The assay was shown to have low inter- and intra-assay variability and conjugated microspheres were shown to remain stable over 12 months. When samples were assayed there was a good correlation of the nonaplex assay with the ELISA. Finally, four bead sets coated with meningococcal polysaccharides (serogroups A, C, Y and W135) were added into the nonaplex assay, with no effect on the pneumococcal or meningococcal IgG levels generated. The pneumococcal nonaplex assay will prove to be a valuable tool to aid in the evaluation of pneumococcal capsular polysaccharide-based vaccines.