Invasive Meningococcal Disease Surveillance Research Articles

Genomic Surveillance of Invasive Meningococcal Disease During a National MenW Outbreak in Australia, 2017-2018.

In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data. Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms. Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia. Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia.

Risk of Invasive Meningococcal Disease in Preterm Infants.

Invasive meningococcal disease (IMD) is most common in the first year of life. We hypothesized that preterm infants may have a higher risk of IMD and more severe disease than term infants. We compared the incidence, demographics, clinical presentation, and outcomes of IMD in preterm compared with term infants during the first 5 years after implementation of a national meningococcal group B vaccine (4CMenB) for infants in England. The UK Health Security Agency conducts enhanced national IMD surveillance with detailed follow-up of all confirmed cases in England. Infants aged <1 year (uncorrected for gestational age) with IMD confirmed between 1 September 2015 and 31 August 2020 were included. There were 393 infant IMD cases (incidence, 12.4/100 000 live births). Among 363 (92.4%) of the infants with known gestational age, the IMD incidence was higher in preterm (<37 weeks' gestation) than in term infants (18.3/100 000 vs 10.9/100 000; incidence rate ratio [IRR], 1.68 [95% confidence interval, 1.23-2.29]; P = .001). The IMD incidence was highest in those born at <32 weeks' gestation (32.9/100 000; incidence rate ratio for <32 weeks' gestation vs term, 3.01 [95% confidence interval, 1.73-5.24]; P ≤ .001). There were no differences in demographics, clinical presentation, rate of intensive care admission, or case-fatality rate, but preterm infants were more likely than term infants to have ≥1 reported sequela (14 of 39 [35.9%] vs 51 of 268 [19.0%]; P = .02). Preterm infants had a higher incidence of IMD than term infants and the IMD incidence was highest in infants born at <32 weeks' gestation. Preterm infants also had a higher risk of IMD sequelae.

Antimicrobial susceptibility profiles and genotyping of Neisseria meningitidis of serogroup C, Italy, 2000-2020.

In Italy the introduction of meningococcal C conjugate vaccine in 2005 has led to a significant reduction of invasive meningococcal disease (IMD) caused by Neisseria meningitidis of serogroup C (MenC). However, this serogroup is still responsible of sporadic cases, clusters and local outbreaks. The study aims to investigate the genotype and antimicrobial susceptibility profile of MenC isolates collected in Italy from 2000 to 2020. Bacterial isolates and biological samples (blood or cerebrospinal fluid) from invasive meningococcal cases are collected and characterized at the National Reference Laboratory for IMD of Istituto Superiore di Sanità. Antimicrobial susceptibility was determined by MIC Test Strip Method and interpreted according to the EUCAST breakpoints guideline. Genotypic characteristics, including multi locus sequence typing (MLST), finetype, and antimicrobial resistance target genes were performed and analyzed using the PubMLST database. Genomic comparison of core genome MLST (cgMLST) of MenC genomes was also carried out. From 2000 to 2020, a total of 665 MenC isolates were investigated for antimicrobial susceptibility and 301 for genotyping. Over two decades, almost all MenC isolates resulted susceptible to antimicrobials with few isolates resulting resistant to ciprofloxacin (N = 2), penicillin G (N = 13), and rifampicin (N = 9), respectively. Molecular typing of MenC obtained from isolates or clinical specimens identified mostly the genotype C:P1.5-1,10-8:F3-6:ST-11(cc11). However, phylogenetic analysis, performed on genomes from MenC isolates, identified two sub lineages, 11.1 and 11.2, among cc11, of which the sub lineage 11.2 was the predominant. Wider application of the genomic analysis and monitoring of antimicrobial susceptibility represent key aspects of IMD surveillance and to monitor the continued evolution of these hyperinvasive strains.

Invasive Disease Due to Neisseria meningitidis: Surveillance and Trends in Israel Prior to and during the COVID-19 Pandemic.

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study's aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998-2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020-2022 vs. 0.9/100,000 in 1998-2019). The number of notified IMD cases declined by 65% in 2020-2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007-2022). Mortality risk markers included cases' age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0-9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs.

Hypervirulent Strains of Neisseria meningitidis and Clinical Manifestations in Children With Invasive Meningococcal Disease.

Hypervirulent clonal complex (cc) have been associated with higher incidence and case fatality rate of invasive meningococcal disease (IMD). The aim of this study was to describe the clinical manifestations of the hypervirulent cc of meningococcus in children. Retrospective study in patients hospitalized by IMD microbiologically confirmed at three children's tertiary health care centers in Santiago, Chile, between 2010 and 2018. Demographic, clinical information and determination of the cc and factor H binding protein (fHbp) alleles were performed. In total 93 cases were evaluated, sequence typing was available for 91 cases, and 87 (95.6%) had a cc assigned; 63.7% were MenW and 31.8% MenB. The median age was 9 months, 67% were male and 18.7% had any comorbidity. A 26.4% presented neurological deficit, 25.3% petechiae and 20% diarrhea. Sixty-seven percent were admitted to the pediatric intensive care unit (PICU) and the case fatality rate was 9.9%. Regarding cc and fHbp alleles, ST11, ST41/44 and allele 22 were the most frequently identified, with 63.7%, 19.8% and 72.5%, respectively. We found statistically significant differences between the cc and presence of petechiae, diagnosis of meningococcemia plus meningitis, admission and days in PICU and advanced support. Allele 22 for fHbp was associated with the absence of petechiae, low suspicion of IMD, less diagnosis of meningitis+meningococcemia, PICU admission, advanced support and adrenal insufficiency. Epidemiological and microbiological surveillance of IMD should integrate clinical and laboratory components, including molecular and genetic characterization, to enrich the dynamic understanding of the clinical evolution of IMD.

Surveillance of invasive meningococcal disease in southern Brazil: considerations of an immunization programme.

Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia worldwide. Changes in serogroup predominance contribute to the unpredictable nature of the disease, with significant health impact. This study aimed to determine the epidemiological profile of IMD in Rio Grande do Sul, Santa Catarina and Paraná, three states in southern Brazil. We analysed 1024 IMD cases that had been confirmed by clinical and/or laboratory criteria and reported to the national information system for notifiable diseases between 2015 and 2019. Additionally, we calculated the proportions of serogroup and incidence by age. Of 1024 cases, 562 (55 %) were caused by serogroup C. Furthermore, serogroup W was responsible for almost half of the cases among children younger than 5 years between 2017 and 2018, with an overall incidence of 1.5 cases/100 000 infants. IMD remains a significant healthcare issue in southern Brazil despite reduced serogroup C incidence after the introduction of the meningococcal C conjugate vaccine into the childhood immunization programme. Changes in disease epidemiology were observed, and serogroup W was the most common serogroup among children younger than 5 years in 2017 and 2018. Although future cost-effectiveness studies are necessary, our results could have future implications for meningococcal vaccination programmes.

Epidemiology of invasive meningococcal disease in Canada, 2012-2019.

A variety of routine childhood and adolescent meningococcal vaccination programs using monovalent (serogroup C) and quadrivalent (A, C, Y, W) conjugate vaccines have been implemented in Canada since 2002, resulting in a decrease in invasive meningococcal disease (IMD) incidence, particularly in serogroup C. Meningococcal vaccines have also been used for outbreak response, including the multicomponent vaccine serogroup B vaccine. This report describes the epidemiology of IMD in Canada from 2012 to 2019. Case data were obtained from the National Enhanced IMD Surveillance System between January 1, 2012 and December 31, 2019. Isolates were sent to the National Microbiology Laboratory for confirmation of serogroup and further studies including phenotype and clonal complex identification. A total of 983 cases of IMD were reported between 2012 and 2019. Overall, the age-adjusted incidence of IMD from 2012 to 2019 was 0.34 cases per 100,000 population per year when standardized to the Canadian 2011 population age distribution (95% CI: 0.32-0.36). Infants younger than one year of age had the highest average age-specific incidence rate (3.6 cases per 100,000 population per year, 95% CI: 2.8-4.3). The highest age-adjusted incidence rate was associated with serogroup B (0.17 cases per 100, 000 population per year, 95% CI: 0.16-0.19). Prior to 2015, most invasive serogroup W isolates were identified as clonal complex 22 (ST-22 CC) and the increase in serogroup W in Canada in recent years has been associated with the replacement of the endemic ST-22 CC with the hyper-virulent ST-11 CC. Invasive meningococcal disease is a rare but severe infection in Canada that mostly affects the very young. Serogroup B continues to account for the greatest proportion of disease. Serogroup W associated with ST-11 CC is becoming a growing contributor of disease in all age groups not protected by serogroup W-containing vaccines.

Timing of meningococcal vaccination with 4CMenB (Bexsero®) in children with invasive meningococcal group B (MenB) disease in England

BackgroundTimely vaccination is critical for providing early protection against meningococcal B (MenB) disease because of the high incidence in early childhood. We assessed the timeliness of vaccination in children with confirmed MenB disease after 4CMenB (a recombinant protein-based vaccine) implementation into the national infant immunisation programme in England. MethodsPublic Health England (PHE) conducts surveillance of invasive meningococcal disease (IMD) in England. Children born since 01 July 2015 who developed MenB disease between 01 September 2015 and 31 August 2019 (four surveillance years) were included in the analysis. ResultsThere were 276 children with laboratory-confirmed MenB disease, including 36 infants who were too young for vaccination, 59 who were eligible for one 4CMenB dose, 104 for two doses and 77 for 3 doses before they developed MenB disease. Prior to developing MenB disease, there were 59 opportunities for vaccination with two 4CMenB doses in 48/104 (46.5%) eligible infants and 41 opportunities in 28/77 (36.6%) children aged ≥ 1 year who were under-immunised. A schedule with a shorter interval at 8 and 12 weeks of age, compared to the current schedule at 8 and 16 weeks, had the potential to offer an additional 4CMenB dose to 35/58 infants (58.6%) who developed MenB disease between 10 and 18 weeks of age. ConclusionsA high proportion of infants and toddlers with laboratory-confirmed MenB disease had not received their scheduled 4CMenB vaccine prior to developing MenB disease. An infant priming schedule with a shorter interval of 4 weeks has the potential to provide earlier protection against MenB disease.

Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination

Integrated Genomic Surveillance of Invasive Meningococcal Disease in Scotland 2015-2022, Following the Introduction of Routine Infant MenB Vaccination

Retraction notice: Surveillance of invasive meningococcal disease in the south of Brazil: considerations of immunization programme.

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The Epidemiology of Invasive Meningococcal Disease in the Kingdom of Saudi Arabia: A Narrative Review with Updated Analysis.

Reducing invasive meningococcal disease (IMD) through MenACWY immunization is a critical healthcare strategy in the Kingdom of Saudi Arabia (KSA). Robust IMD surveillance is essential to help assess the need for additional immunization initiatives in target populations. This is particularly important in KSA, where mass gatherings accompanying Hajj/Umrah pilgrimages have been associated with IMD outbreaks within the local KSA population, and subsequent intercontinental spread via returning pilgrims. This narrative review of the published literature describes the changing epidemiology of IMD in KSA to provide a perspective on the impact of current immunization strategies and potential gaps. As recent published surveillance data are lacking, we also evaluated publicly reported data from the KSA Ministry of Health (MoH) for 2012–2019 to inform more recent IMD trends. Between 1995 and 2011, national surveillance data indicate that 1103 IMD cases were reported in KSA: 60% in 2000–2001, involving two (mainly MenW) outbreaks involving KSA citizens/residents and pilgrims focused in Mecca and Medina. Across 2002–2011, 184 cases of IMD were reported, with a higher proportion occurring in KSA citizens/residents, and with less focus within pilgrimage centers than apparent in previous years. Our analysis of MoH data found that, between 2012 and 2019, 44 IMD cases were reported, all in KSA citizens/residents, and chiefly in children or infants. No pilgrimage-associated outbreaks have occurred since 2001. Serogroup data were available for 62.5% of all cases for 2002–2011; MenW (40.0%), MenA (35.7%), and MenB (16.5%). Serogroup data for 2012–2019 remain incompletely reported, and the existing surveillance system could be improved, as some element of underestimation/underreporting of IMD may exist. While existing MenACWY immunization strategies for KSA citizens/residents and visiting pilgrims have been successful in reducing IMD due to specific serogroups, disease due to MenB remains a potential risk, and additional immunization strategies should be considered.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00467-x.

Surveillance of invasive meningococcal disease in the south of Brazil: considerations of immunization programme.

Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia worldwide. The switches in serogroup predominance contribute to the unpredictable nature of the disease with significant health impacts. The aim of this study was to determine the epidemiological profile of IMD in Rio Grande do Sul, Santa Catarina and Paraná, three states in the south of Brazil. All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2015 and 2019 were analysed. Proportions of serogroup and incidence by age were calculated. A total of 17 894 cases of IMD were reported during this period. Of these, 9029 cases (50 %) were due to serogroup C. Furthermore, serogroup W was responsible for almost half of the cases among children younger than 5 years old during 2017 and 2018, with an overall incidence of 33.3 cases per 100 000 infants. Despite the reduction in serogroup C after the introduction of meningococcal C conjugate vaccine into a childhood immunization programme in Brazil, it remains a significant healthcare issue in the south of the country. Changes in disease epidemiology were observed and serogroup W was the most common among children below 5 years of age in 2017 and 2018. Although future cost-effectiveness studies are necessary, our results could have future implications for meningococcal vaccination programmes.

Evaluation of the national surveillance system for invasive meningococcal disease, Italy, 2015-2018.

Enhanced laboratory-based surveillance of invasive meningococcal disease (IMD) in Italy was only assessed indirectly by numerically comparing surveillance data cases with hospital discharge records (HDR). In this study, we evaluated the completeness, timeliness and sensitivity of the IMD surveillance in Italy from 2015 to 2018. Completeness and timeliness were described at the national and subnational level. A capture-recapture analysis was conducted to evaluate the sensitivity and positive predictive value (PPV) using HDR as the external source with a combination of deterministic and probabilistic approaches. The characteristics of the unmatched vs. matched cases were compared using multivariable Poisson modeling. Overall, the completeness of data improved, except for specific variables. Timeliness of notifications also improved to a median of 4 days from onset to reporting. For the years 2015–2017, the sensitivity of the surveillance was estimated at 71.4% and the PPV at 77.5%, changing to 80.6% and 66.9% respectively after removing cases with a secondary meningitis diagnosis. We noted substantial sub-national differences. In 2018 sensitivity was 66.5% (135/203) and the PPV was 79.4% (135/170). The adjusted relative risk of being unmatched in 2015–2017 was higher in cases that were ≥60 years, had missing information or symptom onset in December. The IMD surveillance system overall performs well with completeness and timeliness improving in time. Specific challenges identified for individual variables should guide further improvement. Notwithstanding limitations posed by the comparison database, sensitivity and PPV are promising. The study highlights that promoting etiological ascertainment in people ≥60 years and addressing sub-national challenges are the main current challenges to address.

Meningococcal B vaccine antigen FHbp variants among disease-causing Neisseria meningitidis B isolates, Italy, 2014-2017.

BackgroundTyping of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). We performed a molecular epidemiology study of N. meningitidis serogroup B (MenB) causing IMD in Italy between 2014 and 2017 to describe circulating strains belonging to this serogroup, with particular regards to the two factor H-binding protein (FHbp) subfamilies present in the bivalent MenB vaccine.Materials and methodsA total of 109 culture positive and 46 culture negative MenB samples were collected within the National Surveillance System (NSS) of IMD in Italy and molecularly analyzed by conventional methods.ResultsOverall, 71 MenB samples showed the FHbp subfamily A and 83 the subfamily B. The subfamily variants were differently distributed by age. The most frequent variants, A05 and B231, were associated with cc213 and cc162, respectively. All MenB with the FHbp A05 variant displayed the PorA P1.22,14 and 85.7% of them the FetA F5-5. The majority of MenB with the FHbp B231 variant showed the PorA P1.22,14 (65.4%) and 84.6%, the FetA F3-6.ConclusionMenB circulating in Italy were characterized by a remarkable association between clonal complex and FHbp variants, although a high degree of genetic diversity observed over time. A dynamic trend in clonal complexes distribution within MenB was detected. Our results stress the importance of continued meningococcal molecular surveillance to evaluate the potential vaccine coverage of the available MenB vaccines.

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2017 and 2018: Prospective hospital-based surveillance for serious paediatric conditions.

The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine-preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2017 and 2018. Specialist nurses screened hospital admissions, emergency department (ED) records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia to identify children with the conditions under surveillance. In 2017 and 2018 these included acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal, and invasive Group A streptococcus diseases. An additional social research component was added to evaluate parental attitudes to vaccination. PAEDS captured 1,580 and 925 cases for 2017 and 2018, respectively, across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets; identification of a third human parechovirus outbreak among other infectious diseases linked to ACE; demonstration of variable influenza activity between 2017 and 2018, with vaccine effectiveness (VE) analysis demonstrating that the protection offered through vaccination is season-dependent. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers remained unchanged, with vaccine uptake found to be suboptimal among eligible children under the NIP. Enhanced pertussis surveillance continues to capture controls for VE estimation. Surveillance for invasive meningococcal disease showed predominance for serotype B at 57% over 2 years among 77 cases where serotyping was available, and surveillance for invasive group A streptococcus captured severe disease in children. PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Neisseria meningitidis Strains and Their Predicted Coverage by the 4CMenB Vaccine.

The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%).IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.

Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England

BackgroundIn September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster.MethodsUsing data from enhanced national surveillance of invasive meningococcal disease in England, we evaluated the effect of vaccination on the incidence of meningococcal group B disease during the first 3 years of the program. The effect of vaccination was assessed by comparing the observed incidence of disease with the expected incidence based on the incidence during the 4-year prevaccination period in equivalent cohorts and with the use of disease trends in cohorts of children younger than 5 years of age who were not eligible to receive the vaccine. Vaccine effectiveness was estimated with the use of the indirect screening method.Results4CMenB uptake in England remained consistently high; data from the first 3 months of 2018 showed that 92.5% of children had completed the primary immunizations by their first birthday and 87.9% had received all three doses by 2 years. From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination. The adjusted vaccine effectiveness against meningococcal group B disease was 52.7% (95% CI, −33.5 to 83.2) with a two-dose priming schedule for infants and 59.1% (95% CI, −31.1 to 87.2) with a two-dose priming schedule plus a booster at 1 year). Over the 3-year period, there were 169 cases of meningococcal group B disease in the vaccine-eligible cohorts, and an estimated 277 cases (95% CI, 236 to 323) were prevented.ConclusionsThe 4CMenB program was associated with continued positive effect against meningococcal group B disease in children in England, and protection after three doses of the vaccine was sustained for at least 2 years. (Funded by Public Health England.)

Invasive meningococcal disease: Timing and cause of death in England, 2008–2015

Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia, with death often occurring rapidly after onset of the first symptoms. Later death can also occur, but may be due to other causes, such as underlying comorbidities. The study aimed to assess the timing and cause of death in patients with invasive meningococcal disease (IMD) prior to the introduction of two new meningococcal immunisation programmes in England. Public Health England (PHE) conducts IMD surveillance in England through its national meningococcal reference unit. Laboratory-confirmed IMD cases diagnosed during 2008-2015 were linked to weekly and annual electronic death registration records as well as the Patient Demographic Service (PDS) database. Overall, 6734 of 6808 (99%) laboratory-confirmed IMD cases matched to PDS, including 668 fatalities. Of these, 667 linked to an annual death registration record compared to 405 reports linked to weekly death registrations. In total, 429/667 (64%) of all deaths and 428/502 (85%) of IMD-related deaths occurred within one day of diagnosis. In total, 498/667 (75%) deaths had occured by 30 days after IMD diagnosis and 98% (490/498) of these were IMD-related. Serogroup B contributed to 64% (323/502) of IMD-related deaths, followed by serogroup W (84/502, 17%) and serogroup Y (70/502, 14%). Deaths occurring after 30 days were less likely to be IMD-related, mainly amongst ≥65 year-olds, with malignancy, chronic respiratory and cardiac conditions predominating. Most IMD-related deaths occurred within a day of diagnosis and nearly all IMD-related deaths occurred within 30 days of diagnosis. The rapidity of death highlights the importance of prevention through vaccination.

Variable clinical presentation by the main capsular groups causing invasive meningococcal disease in England

Invasive meningococcal disease (IMD) typically presents as meningitis, septicaemia or both. Atypical clinical presentations are rare but well-described. We aimed to assess the relationship between meningococcal capsular group, age, clinical presentation, diagnosis and outcome among IMD cases diagnosed in England during 2014. Public Health England conducts enhanced national surveillance of IMD in England. Clinical data for laboratory-confirmed MenB, MenW and MenY cases in ≥5 year-olds were used to classify presenting symptoms, diagnosis and outcomes. Multivariable logistic regression was used to assess independent associations between meningococcal capsular group, clinical presentation, gender, age and death. In 2014, there were 340 laboratory-confirmed IMD cases caused by MenB (n = 179), MenW (n = 95) and MenY (n = 66). Clinical presentation with meningitis alone was more prevalent among MenB cases (28%) and among 15-24 year-olds (20%), whilst bacteraemic pneumonia was most prevalent among MenY cases (26%) and among ≥65 year-olds (24%). Gastrointestinal symptoms were recorded preceding or during presentation in 15% (40/269) cases with available information, including 5% (7/140) MenB, 17% (8/47) MenY and 30% (25/82) MenW cases. Upper respiratory tract symptoms were reported in 16% (22/141) MenB, 23% (11/47) MenY and 31% (26/84) MenW cases. Increasing age was also independently associated with bacteraemic meningococcal pneumonia, with no cases among 5-14 year-olds compared to 24% in ≥65 year-olds. Case fatality rates increased with age but no significant associations with death were identified. Healthcare professionals should be aware of the atypical clinical presentations associated with the less prevalent meningococcal capsular groups in different age-groups.

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe

The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.