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Invasive meningococcal disease (IMD), caused by Neisseria meningitidis , can have a fatality rate as high as 10%, even with appropriate treatment. In the UK, penicillin is administered to patients in primary care whilst third generation cephalosporins, cefotaxime and ceftriaxone, are administered in secondary care. The first-choice antibiotic for chemoprophylaxis of close contacts is ciprofloxacin, followed by rifampicin. Immunocompromised individuals are often recommended antibiotic chemoprophylaxis and vaccination due to a greater risk of IMD. Resistance to antibiotics among meningococci is relatively rare, however reduced susceptibility and resistance to penicillin are increasing globally. Resistance to third generation cephalosporins is seldom reported, however reduced susceptibility to both cefotaxime and ceftriaxone has been observed. Rifampicin resistance has been reported among meningococci, mainly following prophylaxis, and ciprofloxacin resistance, whilst uncommon, has also been reported across the globe. The Public Health England Meningococcal Reference Unit receives and characterises the majority of isolates from IMD cases in England, Wales and Northern Ireland. This study assessed the distribution of antibiotic resistance to penicillin, rifampicin, ciprofloxacin and cefotaxime among IMD isolates received at the MRU from 2010/11 to 2018/19 (n = 4,122). Out of the 4,122 IMD isolates, 113 were penicillin-resistant, five were ciprofloxacin-resistant, two were rifampicin-resistant, and one was cefotaxime-resistant. Penicillin resistance was due to altered penA alleles whilst rifampicin and ciprofloxacin resistance was due to altered rpoB and gyrA alleles, respectively. Cefotaxime resistance was observed in one isolate which had an altered penA allele containing additional mutations to those harboured by the penicillin-resistant isolates. This study identified several isolates with resistance to antibiotics used for current treatment and prophylaxis of IMD and highlights the need for continued surveillance of resistance among meningococci to ensure continued effective use.

Invasive meningococcal disease incidence in England declined from 1.93/100,000 persons (1,016 cases) in 2010–11 to 0.95/100,000 (530 cases) in 2018–19 and 0.74/100,000 in 2019–20 (419 cases). During national lockdown for the coronavirus disease pandemic (April–August 2020), incidence was 75% lower than during April–August 2019.

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Reduction in the transmission of Neisseria meningitidis within a population results in fewer invasive disease cases. Vaccination with meningococcal vaccines composed of high weight capsular polysaccharide without carrier proteins has minimal effect against carriage or the acquisition of carriage. Conjugate vaccines, however, elicit an enhanced immune response which serves to reduce carriage acquisition and hinder onwards transmission. Since the 1990s, several meningococcal conjugate vaccines have been developed and, when used in age groups associated with higher carriage, they have been shown to provide indirect protection to unvaccinated cohorts. This herd protective effect is important in enhancing the efficiency and impact of vaccination. Studies are ongoing to assess the effect of protein-based group B vaccines on carriage; however, current data cast doubt on their ability to reduce transmission.

Invasive meningococcal disease (IMD) caused by serogroup W meningococci belonging to the ST-11 complex (MenW:cc11) has been increasing globally since the early 2000s. Penicillin resistance among meningococci due to the production of beta-lactamase remains relatively rare. Isolates displaying resistance and reduced susceptibility to penicillin due to alterations in the penA gene (encoding Penicillin Binding Protein 2) are increasingly reported. In 2016, a penicillin-resistant clade of MenW:cc11 isolates with altered penA genes was identified in Australia. More recently, an increase in penicillin-resistant invasive MenW:cc11 isolates was observed in England. Here, we investigate the distribution of penicillin resistance among English invasive MenW:cc11 isolates. Isolates from IMD cases in England from July 2010 to August 2019 underwent whole genome sequencing and antibiotic susceptibility testing as part of routine surveillance. The PubMLST Neisseria database was used to determine the distribution of penicillin resistance among English MenW:cc11 isolates and to identify other closely related isolates. Twenty-five out of 897 English invasive MenW:cc11 isolates were resistant to penicillin; identified among six distinct sublineages and a singleton. Expansion of the Australian penicillin-resistant clade included isolates from several new countries as well as 20 English isolates. A newly identified penicillin resistance-associated lineage was also identified among several countries. Penicillin resistance among diverse MenW:cc11 isolates is increasing. Surveillance of antibiotic resistance among meningococci is essential to ensure continued effective use.

The UK introduced 4CMenB—a multicomponent vaccine against serogroup B meningococcal disease—into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007–08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014–15, before 4CMenB introduction; compare strain coverage between 2007–08 and 2014–15; and investigate associations between MATS coverage, age, region, and disease outcomes. Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014–15 were assayed using MATS and compared with 2007–08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014–15 English cases. In 2014–15, 165 of 251 (66%; 95% CI 52–80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57–87) in 2007–08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007–08 to 31% (78 of 251) in 2014–15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease. In 2014–15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes. Public Health England, GlaxoSmithKline.

Neisseria meningitidis is a cause of meningitis and outbreaks of it among young adults, especially college students. Rates of nasopharyngeal colonization and prevalence of specific capsular groups vary with age, geography as well as time, and may be influenced by meningococcal vaccination. The objective of this study was to measure the change in colonization rate, and define which meningococcal genogroups were present, in college students over a 3-month semester. This was a prospective, longitudinal cohort study with sequential oropharyngeal swabbing among college students at the University of Louisville (UofL) in Louisville, Kentucky from August to November 2022. Participants were ≥18 years of age and were enrolled within 48 hours of moving to campus-affiliated housing. Oropharyngeal swabs were collected at enrollment, one month and at three months. Samples were screened for N. meningitidis, and isolates were characterized using phenotypic and genotypic methods. Behavior questionnaires were obtained at each visit to identify risk factors for N. meningitidis colonization. A total of 1047 participants were seen initially, of whom 821 attended all three visits. The baseline colonization rate was 3.5% followed by 3.9% after one month and 5.7% after three months. The genogroups of recovered isolates were capsule null (48%), B (38%; of which 11% were expressing capsule) and E (12%). No genogroup ACWY isolates were recovered. A total of 36% of participants had a history of receiving at least one MenB vaccine dose and 74% had a history of receiving at least one MenACWY vaccine. Risk factors for N. meningitidis nasopharyngeal carriage included being a second-year student, living on campus for the second year, smoking/vaping, kissing and sexual contact. An increase in N. meningitidis colonization over the 3-month semester was observed from 3.5% to 5.7%. The overall proportion of student carriers was significantly lower, and there were no genogroup A, C, W or Y strains isolated compared to studies conducted prior to the availability of meningococcal vaccines and the COVID-19 pandemic. However, genogroup B carriage, transmission and acquisition were almost identical to pre-COVID pandemic studies. This study reinforces the importance of periodic epidemiological monitoring of carriage as well as disease.

Background To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. Methods Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008–2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. Results A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. Conclusions In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Abstract Background Since 2009, increases in the incidence of invasive meningococcal disease have occurred in the United Kingdom due to a sublineage of the Neisseria meningitidis serogroup W ST-11 clonal complex (hereafter, the “original UK strain”). In 2013, a descendent substrain (hereafter, the “2013 strain”) became the dominant disease-causing variant. Multiple outer-membrane proteins of meningococci are subject to phase-variable switches in expression due to hypermutable simple-sequence repeats. We investigated whether alterations in phase-variable genes may have influenced the relative prevalence of the original UK and 2013 substrains, using multiple disease and carriage isolates. Methods Repeat numbers were determined by either bioinformatics analysis of whole-genome sequencing data or polymerase chain reaction amplification and sizing of fragments from genomic DNA extracts. Immunoblotting and sequence-translation analysis was performed to identify expression states. Results Significant increases in repeat numbers were detected between the original UK and 2013 strains in genes encoding PorA, NadA, and 2 Opa variants. Invasive and carriage isolates exhibited similar repeat numbers, but the absence of pilC gene expression was frequently associated with disease. Conclusions Elevated repeat numbers in outer-membrane protein genes of the 2013 strain are indicative of higher phase-variation rates, suggesting that rapid expansion of this strain was due to a heightened ability to evade host immune responses during transmission and asymptomatic carriage. Increased numbers of repeats were observed in multiple phase-variable genes encoding outer-membrane proteins during evolution of the Neisseria meningitidis hypervirulent MenW ST-11 clonal complex, indicative of a heightened potential for immune evasion during transmission and carriage of this pathogen.

Factor H binding protein (fHbp) is a major protective antigen in 4C-MenB (Bexsero®) and Trumenba®, two serogroup B meningococcal vaccines, wherein expression level is a determinant of protection. Examination of promoter-containing intergenic region (IGR) sequences indicated that nine fHbp IGR alleles covered 92% of 1,032 invasive meningococcal strains with variant 1 fHbp alleles. Relative expression values for fHbp were determined for 79 meningococcal isolates covering ten IGR alleles by quantitative reverse transcriptase polymerase chain reaction (qRT PCR). Derivation of expression clusters of IGR sequences by linear regression identified five expression clusters with five nucleotides and one insertion showing statistically associations with differences in expression level. Sequence analysis of 273 isolates examined by the Meningococcal Antigen Typing Scheme, a sandwich ELISA, found that coverage depended on the IGR expression cluster and vaccine peptide homology combination. Specific fHbp peptide-IGR expression cluster combinations were designated as 'at risk' for coverage by 4C-MenB and were detected in multiple invasive meningococcal disease cases confirmed by PCR alone and occurring in partially-vaccinated infants. We conclude that sequence-based analysis of IGR sequences is informative for assessing protein expression and has utility for culture-independent assessments of strain coverage by protein-based vaccines.