Serogroup B Invasive Meningococcal Disease in Older Adults Identified by Genomic Surveillance, England, 2022-2023.

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.

Beyond the usual suspects: Reviewing infections caused by typically-commensal Neisseria species.

OBJECTIVE: Few data outside of individual case reports are available on non-meningococcal, non-gonococcal species of Neisseria as causative agents of invasive disease. This review collates disease, organism and patient information from case reports on the topic. METHODS: A literature search was performed examining articles describing diseases caused by non-meningococcal and non-gonococcal Neisseria. FINDINGS: Neisseria present as opportunistic pathogens causing a wide variety of diseases including serious presentations, endocarditis being the most common condition described and N. mucosa the most commonly presenting pathogen overall. Disease may occur in otherwise healthy patients, although risk factors for infection include recent surgery, an immunocompromised state, poor oral health, and intravenous drug use. CONCLUSIONS: Commensal Neisseria infections are rare but can present serious invasive diseases. Further research is required to determine why some species cause disease more than others or why some are inclined towards particular manifestations.

Epidemiological and strain characteristics of invasive meningococcal disease prior to, during and after COVID-19 pandemic restrictions in England.

OBJECTIVES: In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal disease in the three years prior to the COVID-19 pandemic, and the three years immediately after the introduction of restrictions. METHODS: The UK Health Security Agency conducts national meningococcal disease surveillance in England consisting of laboratory-based case confirmation with strain characterisation by culture and/or molecular detection, as well as clinical follow-up of all cases. RESULTS: In the pre-pandemic period, 554-742 IMD cases were laboratory-confirmed per year. MenB caused 57.2% of cases, followed by MenW (22.7%), MenY (10.6%) and MenC (7.7%). The introduction of restrictions in late March 2020 led to a 73% reduction in IMD. After the removal of restrictions in 2021, a resurgence in MenB was observed, primarily in teenagers and young adults. During the following winter period (2022/23), MenB disease increased to the highest level since 2012 with cases rising across multiple age groups, however, cases in young children eligible for MenB vaccination remained lower than prior to the pandemic. MenACWY cases remained very low throughout the pandemic period. CONCLUSIONS: Once pandemic restrictions in England were removed, MenB quickly rebounded- initially driven by a resurgence in teenagers/young adults, but later among other age groups. MenACWY cases remain very low due to the protection afforded by the adolescent MenACWY conjugate vaccine programme.

Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study.

BACKGROUND: In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes. METHODS: In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3-6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021. FINDINGS: Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5-6 months to 1-3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae. INTERPRETATION: Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination. FUNDING: UK Health Security Agency.

Evaluation of Dried Blood and Cerebrospinal Fluid Filter Paper Spots for Storing and Transporting Clinical Material for the Molecular Diagnosis of Invasive Meningococcal Disease.

To improve the storage and transport of clinical specimens for the diagnosis of Neisseria meningitidis (Nm) infections in resource-limited settings, we have evaluated the performance of dried blood spot (DBS) and dried cerebrospinal fluid spot (DCS) assays. DBS and DCS were prepared on filter paper from liquid specimens previously tested for Nm in the United Kingdom. Nm was detected and genogrouped by real-time PCR performed on crude genomic DNA extracted from the DBS (n = 226) and DCS (n = 226) specimens. Targeted whole-genome sequencing was performed on a subset of specimens, DBS (n = 4) and DCS (n = 6). The overall agreement between the analysis of liquid and dried specimens was (94.2%; 95% CI 90.8−96.7) for blood and (96.4%; 95% CI 93.5−98.0) for cerebrospinal fluid. Relative to liquid specimens as the reference, the DBS and DCS assays had sensitivities of (89.1%; 95% CI 82.7−93.8) and (94.2%; 95% CI 88.9−97.5), respectively, and both assays had specificities above 98%. A genogroup was identified by dried specimen analysis for 81.9% of the confirmed meningococcal infections. Near full-length Nm genome sequences (>86%) were obtained for all ten specimens tested which allowed determination of the sequence type, clonal complex, presence of antimicrobial resistance and other meningococcal genotyping. Dried blood and CSF filter spot assays offer a practical alternative to liquid specimens for the molecular and genomic characterisation of invasive meningococcal diseases in low-resource settings.

An analysis of Neisseria meningitidis strains causing meningococcal septic arthritis in England and Wales: 2010-2020.

OBJECTIVES: To analyze clinical meningococcal strains associated with meningococcal septic arthritis cases in England and Wales, and to identify associations between patient age, the synovial joint affected and strain characteristics. METHODS: IMD cases confirmed by the Meningococcal Reference Unit (UK Health Security Agency) between January 2010 and December 2020 were included in the analysis. Septic arthritis cases were defined as those featuring detection and/or isolation of N. meningitidis from an articular site. Capsular grouping was performed by serology on clinical isolates and/or real-time PCR on clinical samples. RESULTS: We identified 162 cases of meningococcal septic arthritis, representing 2% of all invasive meningococcal disease cases during the study period. The knee and the hip were the most commonly affected joints, with the former significantly more frequent in adults and the latter seen more commonly in children and adolescents. Group B strains were between 2 and 6 times less likely to cause septic arthritis in relation to groups W, C and Y strains. CONCLUSIONS: Meningococcal septic arthritis remains a rare manifestation of invasive meningococcal disease. Strain and age associations identified in this study remain unexplained. Future analyzes including clinical case information may help to explain these findings.

Unencapsulated penicillin-resistant Neisseria meningitidis ST-53 clonal complex strain causing symptomatic proctitis in an HIV-negative man who has sex with men: A case report.

We report a case of Neisseria meningitidis symptomatic proctitis in an HIV-negative man who has sex with men attending the genitourinary clinic in Malta. The proctitis was caused by a rare clinical unencapsulated penicillin-resistant N. meningitidis strain of the ST-53 clonal complex.

Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme.

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.

Invasive serogroup B meningococci in England following three years of 4CMenB vaccination - First real-world data.

OBJECTIVES: In 2015 the UK became the first country to implement the meningococcal B (MenB) vaccine, 4CMenB, into the national infant program. 4CMenB is expected to cover meningococci expressing sufficient levels of cross-reactive proteins. This study presents clonal complex, 4CMenB antigen genotyping, and 4CMenB coverage data for all English invasive MenB isolates from 2014/15 (1 year pre-vaccine) through 2017/18 and compares data from vaccinated and unvaccinated ≤3 year olds. METHODS: Vaccine coverage of all invasive MenB isolates from 2014/15 to 2017/18 (n = 784) was analysed using the Meningococcal Antigen Typing System. Genotyping utilised the Meningococcus Genome Library. RESULTS: Among ≤3 year olds, proportionally fewer cases in vaccinees (1, 2 or 3 doses) were associated with well-covered strains e.g. cc41/44 (20.5% versus 36.4%; P<0.01) and antigens e.g. PorA P1.4 (7.2% versus 17.3%; P = 0.02) or fHbp variant 1 peptides (44.6% vs 69.1%; P<0.01). Conversely, proportionally more cases in vaccinees were associated with poorly-covered strains e.g. cc213 (22.9% versus 9.6%; P<0.01) and antigens e.g. variant 2 or 3 fHbp peptides (54.2% versus 30.9%; P<0.01). CONCLUSIONS: 4CMenB reduces disease due to strains with cross-reactive antigen variants. No increase in absolute numbers of cases due to poorly covered strains was observed in the study period.

Antibiotic resistance among invasive Neisseria meningitidis isolates in England, Wales and Northern Ireland (2010/11 to 2018/19).

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, 2011-2020, and Impact of the COVID-19 Pandemic, England.

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.

Colistin Sensitivity and Factor H-Binding Protein Expression among Commensal Neisseria Species.

Many bacterial carriage studies utilize colistin-containing media to select for Neisseria meningitidis among the diverse human pharyngeal milieu. These studies commonly report the isolation of Neisseria commensal species, with carriage rates of around 1% or less typically observed. Here, we describe the isolation of N. cinerea and N. polysaccharea from pharyngeal swabs using nonselective agar and confirm they are unable to grow on colistin-containing media. We also demonstrated colistin sensitivity among archived Neisseria commensal strains, including N. cinerea, N. polysaccharea, N. mucosa, and N. subflava. The distribution of lptA among these strains indicated that, while the phosphoethanolamine (PEA) transferase encoded by this gene confers colistin resistance, other mechanisms may lead to reduced susceptibility in some lptA-deficient strains. The majority of the N. cinerea and N. polysaccharea isolates expressed medium to very high levels of factor H-binding protein (fHbp), an important meningococcal vaccine antigen. Sequence analysis showed that the commensal fHbp peptide variants were similar in sequence to fHbp variants typically observed among invasive meningococci. Altogether, these results not only suggest that Neisseria commensal strains could be carried at much higher rates than previously reported but also raise questions about the impact of protein-based meningococcal vaccines on these unencapsulated commensals. IMPORTANCE This study highlights the need for further work to accurately determine the pharyngeal carriage prevalence of Neisseria commensal bacteria (e.g., N. cinerea and N. polysaccharea) among the general population. Previous studies have clearly demonstrated the suppressive effect these commensal species can have on meningococcal colonization, and so the carriage prevalence of these species could be an important factor in the spread of meningococci through the population. Furthermore, the surface expression of the meningococcal vaccine antigen factor H-binding protein by many of these commensal strains could have important implications for the use of fHbp-containing vaccines. Carriage of these commensal species may influence the immune response to these vaccines, or conversely, the immune response elicited by vaccination may induce clearance of these potentially important members of the pharyngeal niche.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Increase in penicillin-resistant invasive meningococcal serogroup W ST-11 complex isolates in England.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Penicillin resistance among diverse MenW:cc11 isolates is increasing. Surveillance of antibiotic resistance among meningococci is essential to ensure continued effective use.

First Real-world Evidence of Meningococcal Group B Vaccine, 4CMenB, Protection Against Meningococcal Group W Disease: Prospective Enhanced National Surveillance, England.

BACKGROUND: 4CMenB is a protein-based meningococcal B vaccine, but the vaccine antigens may be present on non-group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunization program, alongside an emergency adolescent meningococcal ACWY (MenACWY) program to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST-11 clonal complex. The adolescent program aimed to provide direct protection for adolescents and indirect protection across the population. METHODS: Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during 4 years before and 4 years after implementation of both vaccines were analyzed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB program along with the indirect impact of the adolescent MenACWY program in children eligible for 4CMenB but not MenACWY. RESULTS: Model estimates showed 69% (adjusted incidence rate ratio [aIRR], .31; 95% CI, .20-.67) and 52% (aIRR, .48; 95% CI, .28-.81) fewer MenW cases than predicted among age-cohorts that were fully- and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in <5-year-olds. 4CMenB directly prevented 98 (95% CI, 34-201) cases, while the MenACWY program indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over 4 years. Disease severity was similar in 4CMenB-immunized and unimmunized children. CONCLUSIONS: This is the first real-world evidence of direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

Herd Protection against Meningococcal Disease through Vaccination.

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.

Outbreak strain characterisation and pharyngeal carriage detection following a protracted group B meningococcal outbreak in adolescents in South-West England.

Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaDB) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.

Invasive meningococcal disease in patients with complement deficiencies: a case series (2008-2017).

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.