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Introduction: Despite its impact on a patient's life, there is a paucity of evidence on the humanistic burden of invasive meningococcal disease (IMD) due to serogroup B (MenB) in Spain. This study estimates the total quality-adjusted life-year (QALY) loss due to MenB-IMD in Spain from a societal perspective., Materials and Methods: A previously published incidence-based Excel tool adapted to the Spanish setting was used to estimate total QALY losses over a patient's lifetime horizon, including direct and indirect impact on patients and families/caregivers, respectively. A 3% discount rate was applied, and a deterministic and probabilistic sensitivity analyses were performed to evaluate uncertainty and assumptions used for the base case., Results: The total discounted QALY loss for a hypothetical cohort of 142 cases of MenB-IMD was 572.44 QALYs (4.03/case). Direct loss (attributable to patients) represented 81.2% of the total loss (464.54 QALYs; 3.27/case) and indirect loss (caused to relatives/ caregivers) represented 18.8% (108.90 QALYs; 0.76/case). Sequelae had the highest impact on QALY loss for both patients (60.5%) and relatives/caregivers (84.6%). Children <5 years of age (YOA) accounted for 47.8% of the total QALY loss. Mortality accounted for 17.62 QALY loss per death. The discount rate parameter showed the highest influence on results and the probabilistic sensitivity analysis revealed a 98.0% probability of total QALY loss achieving the point estimate., Conclusions: The results emphasize that the humanistic burden associated with a MenB case is mainly driven by its sequelae, impacting the patients and their relatives/caregivers., Competing Interests: Declaration of competing interest AG, LAV-A, GN and CGI are employees of GSK. LAV-A, GN and CGI hold financial equities in GSK. EdG was a GSK employee at the time of the study was performed. NB is a freelance consultant for GSK. All authors declare no other financial and non-financial relationships and activities., (Copyright © 2024 GSK. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The incidence of serogroup C invasive meningococcal disease (IMD) has decreased since the introduction of systematic vaccination in 2000. The aim of this study is to determine the number of serogroup C IMD cases diagnosed since then and the vaccine failures., Patients and Methods: A retrospective analysis was performed on patients diagnosed with IMD by culture or polymerase chain reaction (PCR) in a maternity and childhood hospital in Barcelona between 2001 and 2018. An analysis was made of the number of vaccine doses and the age received, as well as on the medical records and vaccine cards., Results: There were 128 confirmed cases of IMD (7.1 cases/year; 70.3 in <5 years). The serogroup was studied in 125 (97.6%) cases, in which 103 (82.4%) were B, 10 (8%) were C, one (0.8%) was 29E, and one (0.8%) was Y, and only 10 (8%) were not able to be serogrouped. Of the 10 patients with serogroup C, 4 were not vaccinated, and in 3, the course was not complete as regards the number of doses. The other 3 received the complete course according to age and current calendar, and thus were considered vaccine failures. A total of 6 patients died (mortality rate: 4.7%), 5 due to serogroup B (mortality: 4.8%), and one due to serogroup C (mortality: 10%)., Conclusions: Serogroup C only represented 8% of IMD cases in the period studied, with 30% of cases due to this serogroup being vaccine failures., (Copyright © 2020 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Neisseria meningitidis is a human-restricted bacterium that can invade the bloodstream and cross the blood-brain barrier resulting in life-threatening sepsis and meningitis. Meningococci express a cytoplasmic peroxiredoxin-glutaredoxin (Prx5-Grx) hybrid protein that has also been identified on the bacterial surface. Here, recombinant Prx5-Grx was confirmed as a plasminogen (Plg)-binding protein, in an interaction which could be inhibited by the lysine analogue ε-aminocapronic acid. rPrx5-Grx derivatives bearing a substituted C-terminal lysine residue (rPrx5-Grx K244A ), but not the active site cysteine residue (rPrx5-Grx C185A ) or the sub-terminal rPrx5-Grx K230A lysine residue, exhibited significantly reduced Plg-binding. The absence of Prx5-Grx did not significantly reduce the ability of whole meningococcal cells to bind Plg, but under hydrogen peroxide-mediated oxidative stress, the N. meningitidis Δpxn5-grx mutant survived significantly better than the wild-type or complemented strains. Significantly, using human whole blood as a model of meningococcal bacteremia, it was found that the N. meningitidis Δpxn5-grx mutant had a survival defect compared with the parental or complemented strain, confirming an important role for Prx5-Grx in meningococcal pathogenesis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Limited data is available to describe clinical characteristics, long-term outcomes, healthcare resource use and the attributable costs of invasive meningococcal disease (IMD) in Germany. We aimed to examine demographic and clinical characteristics as well as healthcare resource use and related costs., Methods: We conducted a retrospective cohort study based on the InGef database in patients with IMD between 2009 and 2015. Cases were identified based on hospital main discharge diagnoses of IMD. Demographics, clinical characteristics, 30-day and 1-year mortality as well as IMD-related complications and sequelae in IMD cases were examined. In addition, short and long-term costs and healthcare resource use in IMD cases were analyzed and compared to an age- and sex-matched control group without IMD., Results: The study population comprised 164 IMD cases between 2009 and 2015. The mean length of the IMD-related hospitalization was 13 days and 38% of all cases presented with meningitis only, 35% with sepsis only, 16% with both and 11% with other IMD. The 30-day and one-year mortality were 4.3% and 5.5%, respectively. Approximately 13% of IMD cases had documented IMD-related complications at hospital discharge and 24% suffered from sequelae during follow-up. The IMD-related hospitalization was associated with mean costs of € 9,620 (standard deviation: € 22,197). The difference of mean costs between IMD cases and matched non-IMD controls were € 267 in the first month and € 1,161 from one month to one year after discharged from IMD-related hospitalization. During the later follow-up period, the mean overall costs and costs associated with individual healthcare sectors were also higher for IMD cases without reaching statistical significance., Conclusions: IMD resulted in severe complications and sequelae and was associated with extensive costs and increased healthcare resource use in Germany, especially in the first year after IMD diagnosis and due the IMD-related hospitalization., Competing Interests: This work was supported by Pfizer Inc. The funder provided support in the form of salaries for authors (LH, SJ), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. DH is employed by WIG2 which received funding from Pfizer Inc for the execution of the study and manuscript preparation. NS and ODH are employed by InGef which acted as subcontractor and received funding from WIG2 for the execution of the study and manuscript preparation. LH and SJ are employees of Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.“

The present study describes the epidemiology of invasive meningococcal disease (IMD) in Greece for the period 2006-2016. Combined data from notified and laboratory-confirmed IMD cases were obtained from the two involved National Centres (Epidemiology and Reference Laboratory). Laboratory identification and typing was carried out by both conventional (culture) and molecular methods (PCR, MLST, PorA, and FetA typing). A total of 796 IMD cases were notified; of those, 720 (91%) were laboratory confirmed. Overall, a decline on the annual incidence of confirmed cases was observed, ranging from 0.91 (2006) to 0.47 (2016) /100,000. A similar trend was observed in most age groups especially in children 0-4 years (7.7 to 2.9/100,000), with the exception of an increase in the incidence rate in adults > 20 years (0.21 to 0.32/100,000). The overall case fatality rate was 6.5% (52/796), annual range 2-13%. Among 658 strains which were typed by sero/genogroup, 80% were identified as MenB (annual range 65-92%); however, a decline was observed in MenB incidence from 5.3 (2006) to 2.7 (2016), among infants and toddlers, while MenW (1%), MenY (2%), and MenA (1%) remained low. During the 11 years, the annual incidence of IMD declined by 50%, especially in the 0-4-year age group, due mainly to MenB. Continuous surveillance of IMD is important for the development of future vaccination and public health policies.

GNA2091 is one of the components of the 4-component meningococcal serogroup B vaccine (4CMenB) vaccine and is highly conserved in all meningococcal strains. However, its functional role has not been fully characterized. Here we show that nmb2091 is part of an operon and is cotranscribed with the nmb2089, nmb2090 , and nmb2092 adjacent genes, and a similar but reduced operon arrangement is conserved in many other gram-negative bacteria. Deletion of the nmb2091 gene causes an aggregative phenotype with a mild defect in cell separation; differences in the outer membrane composition and phospholipid profile, in particular in the phosphoethanolamine levels; an increased level of outer membrane vesicles; and deregulation of the zinc-responsive genes such as znuD . Finally, the ∆2091 strain is attenuated with respect to the wild-type strain in competitive index experiments in the infant rat model of meningococcal infection. Altogether these data suggest that GNA2091 plays important roles in outer membrane architecture, biogenesis, homeostasis, and in meningococcal survival in vivo , and a model for its role is discussed. These findings highlight the importance of GNA2091 as a vaccine component.-Seib, K. L., Haag, A. F., Oriente, F., Fantappiè, L., Borghi, S., Semchenko, E. A., Schulz, B. L., Ferlicca, F., Taddei, A. R., Giuliani, M. M., Pizza, M., Delany, I. The meningococcal vaccine antigen GNA2091 is an analogue of YraP and plays key roles in outer membrane stability and virulence.

Introduction:  Meningococcal septicemia is not merely an acute disease with a high lethality, but patients surviving the fulminant phase can suffer from serious long-term sequelae., Materials and Methods:  The records of 165 patients admitted to the hospital from 1968 to 2008 with the diagnosis of meningococcal septicemia were retrospectively reviewed for early signs at presentation, intensive care management, acute symptoms, the necessity of plastic and orthopaedic surgical management, and long-term orthopaedic sequelae. Possible predictors of these conditions were determined., Results:  Overall lethality was 17.5%, and mean time of hospitalization time was 28 days. Integument involvement occurred in 45%, often resulting in the necessity of plastic surgical procedures. Young age is a significant indicator or skin involvement. Amputations were necessary in 9% of all cases, affecting the lower extremities more often than the upper extremities. Six percent of all children suffered from long-term orthopaedic sequelae, such as growth retardation and angular deformities, appearing up to 11 years (mean 4.9 years) after onset of the acute disease. The incidence of amputations and long-term orthopaedic sequelae correlated significantly with severity of the disease., Conclusion:  Meningococcal septicemia can entail devastating long-term consequences in children surviving the acute phase of the disease. Sequelae may become apparent only years later and cause further damage. To prevent this, a systematic follow-up till adulthood is necessary., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

The role of pre-hospital antibiotic therapy in invasive meningococcal diseases remains unclear with contradictory data. The aim was to determine this role in the outcome of invasive meningococcal disease. Observational cohort study of patients with/without pre-hospital antibiotic therapy in invasive meningococcal disease attended at the Hospital Universitari de Bellvitge (Barcelona) during the period 1977-2013. Univariate and multivariate analyses of mortality, corrected by propensity score used as a covariate to adjust for potential confounding, were performed. Patients with pre-hospital antibiotic therapy were also analyzed according to whether they had received oral (group A) or parenteral antibiotics (early therapy) (group B). Five hundred twenty-seven cases of invasive meningococcal disease were recorded and 125 (24%) of them received pre-hospital antibiotic therapy. Shock and age were the risk factors independently related to mortality. Mortality differed between patients with/without pre-hospital antibiotic therapy (0.8% vs. 8%, p = 0.003). Pre-hospital antibiotic therapy seemed to be a protective factor in the multivariate analysis of mortality (p = 0.038; OR, 0.188; 95% CI, 0.013-0.882). However, it was no longer protective when the propensity score was included in the analysis (p = 0.103; OR, 0.173; 95% CI, 0.021-1.423). Analysis of the oral and parenteral pre-hospital antibiotic groups revealed that there were no deaths in early therapy group. Patients able to receive oral antibiotics had less severe symptoms than those who did not receive pre-hospital antibiotics. Age and shock were the factors independently related to mortality. Early parenteral therapy was not associated with death. Oral antibiotic therapy in patients able to take it was associated with a beneficial effect in the prognosis of invasive meningococcal disease.

Meningococcal disease was first clinically characterised by Gaspard Vieusseux in 1805, and its causative agent was identified by Anton Weichselbaum in 1887, who named it Diplococcus intracellularis menigitidis. From the beginning, the disease was dreaded because of its epidemic nature, predilection for previously healthy children and adolescents, and high mortality. In the last decade of the 19th century, the concept of serum therapy for toxin-related bacterial diseases was identified. This concept was applied to meningococcal disease therapy, in an independent way, by Wilhelm Kolle, August von Wasserman, and Georg Jochmann in Germany, and Simon Flexner in the USA, resulting in the first successful approach for the treatment of meningococcal disease. During the first three decades of the 20th century, serum therapy was the standard treatment for meningococcal disease. With the advent of sulphamides first and then antibiotics, serum therapy was abandoned. The great challenges that infectious diseases medicine is facing and the awaiting menaces in the future in terms of increasing antibiotic resistance, emergence of new pathogens, and re-emergence of old ones without effective therapy, make passive immunotherapy a promising tool. Acknowledging the achievements of our predecessors might teach us some lessons to bring light to our future., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Invasive meningococcal disease (IMD) is endemic to South Africa, where vaccine use is negligible. We describe the epidemiology of IMD in South Africa., Methods: IMD cases were identified through a national, laboratory-based surveillance program, GERMS-SA, from 2003-2016. Clinical data on outcomes and human immunodeficiency virus (HIV) statuses were available from 26 sentinel hospital sites. We conducted space-time analyses to detect clusters of serogroup-specific IMD cases., Results: Over 14 years, 5249 IMD cases were identified. The incidence was 0.97 cases per 100 000 persons in 2003, peaked at 1.4 cases per 100 000 persons in 2006, and declined to 0.23 cases per 100 000 persons in 2016. Serogroups were confirmed in 3917 (75%) cases: serogroup A was present in 4.7% of cases, B in 23.3%, C in 9.4%; W in 49.5%; Y in 12.3%, X in 0.3%; Z in 0.1% and 0.4% of cases were non-groupable. We identified 8 serogroup-specific, geo-temporal clusters of disease. Isolate susceptibility was 100% to ceftriaxone, 95% to penicillin, and 99.9% to ciprofloxacin. The in-hospital case-fatality rate was 17% (247/1479). Of those tested, 36% (337/947) of IMD cases were HIV-coinfected. The IMD incidence in HIV-infected persons was higher for all age categories, with an age-adjusted relative risk ratio (aRRR) of 2.5 (95% confidence interval [CI] 2.2-2.8; P < .001) from 2012-2016. No patients reported previous meningococcal vaccine exposure. Patients with serogroup W were 3 times more likely to present with severe disease than those with serogroup B (aRRR 2.7, 95% CI 1.1-6.3); HIV coinfection was twice as common with W and Y diseases (aRRR W = 1.8, 95% CI 1.1-2.9; aRRR Y = 1.9, 95% CI 1.0-3.4)., Conclusions: In the absence of significant vaccine use, IMD in South Africa decreased by 76% from 2003-2016. HIV was associated with an increased risk of IMD, especially for serogroup W and Y diseases., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction and Aims: Since 2013 MenC and MenW disease incidence and associated mortality rates have increased in the Republic of Ireland. From 2002/2003 to 2012/2013, the average annual MenC incidence was 0.08/100,000, which increased to 0.34/100,000 during 2013/2014 to 2017/18, peaking in 2016/17 (0.72/100,000) with an associated case fatality rate (CFR) of 14.7%. MenW disease incidence has increased each year from 0.02/100,000 in 2013/2014, to 0.29/100,000 in 2017/18, with an associated CFR of 28.6%. We aimed to characterise and relate recent MenC isolates to the previously prevalent MenC:cc11 ET-15 clones, and also characterise and relate recent MenW isolates to the novel 'Hajj' clones., Methods: Using WGS we characterised invasive (n = 74, 1997/98 to 2016/17) and carried (n = 16, 2016/17) MenC isolates, and invasive (n = 18, 2010/11 to 2016/17) and carried (n = 15, 2016/17) MenW isolates. Genomes were assembled using VelvethOptimiser and stored on the PubMLST Neisseria Bacterial Isolate Genome Sequence Database. Isolates were compared using the cgMLST approach., Results: Most MenC and MenW isolates identified were cc11. A single MenC:cc11 sub-lineage contained the majority (68%, n = 19/28) of recent MenC:cc11 disease isolates and all carried MenC:cc11 isolates, which were interspersed and distinct from the historically significant ET-15 clones. MenW:cc11 study isolates clustered among international examples of both the original UK 2009 MenW:cc11, and novel 2013 MenW:cc11clones., Conclusions: We have shown that the majority of recent MenC disease incidence was caused by strain types distinct from the MenC:cc11 ET-15 clone of the late 1990s, which still circulate but have caused only sporadic disease in recent years. We have identified that the same aggressive MenW clone now established in several other European countries, is endemic in the RoI and responsible for the recent MenW incidence increases. This data informed the National immunisation Advisory Committee, who are currently deliberating a vaccine policy change to protect teenagers., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Invasive meningococcal disease (IMD) is uncommon but still causes considerable public health burden due to its high mortality and morbidity. This review aims to quantitatively synthesise all published evidence pertinent to mortality caused by IMD and assess the effect of age and serogroup on case fatality rates (CFRs)., Methods: The PubMed and Embase databases, and the Cochrane Library were searched. Articles reporting national CFRs and published in English between January 2000 and May 2018 were eligible. The studies reporting mortality resulting from a specific symptom of IMD (e.g. meningococcal meningitis) were excluded. Mixed-effects logistic regression with a restricted cubic spline was used to analyse CFRs as a function of age. Random-effects meta-analyses were performed to estimate an overall CFR and CFRs by serogroup., Results: Among 48 eligible studies reporting national CFRs, 40 studies were included in meta-analyses representing 163,758 IMD patients. CFRs ranged from 4.1% to 20.0% with the pooled overall CFR of 8.3% (95% confidence interval (CI): 7.5-9.1%). Serogroup B was associated with a lower pooled CFR (6.9% (95%CI: 6.0-7.8%)) than other serogroups (W: 12.8% (95%CI: 10.7-15.0%); C: 12.0% (95%CI: 10.5-13.5%); Y: 10.8% (95%CI: 8.2-13.4%)). The meta-analysis was not performed for serogroup A (MenA) cases due to a small number of MenA patients who were enrolled in eligible studies. For laboratory confirmed IMD cases, the predicted CFR was 9.0% in infants, gradually decreased to 7.0% in 7-year olds, subsequently increased to 15.0% in young adults aged 28 years, stabilised between 15 and 20% in mid-aged adults and reached a high in elderly people., Conclusions: Our findings can provide useful information for better understanding the mortality risks, and quantifying the burden associated with IMD mortality., (Copyright © 2019. Published by Elsevier Ltd.)

Background: While overall rates of meningococcal disease have been declining in the United States for the past several decades, New York City (NYC) has experienced two serogroup C meningococcal disease outbreaks in 2005-2006 and in 2010-2013. The outbreaks were centered within drug use and sexual networks, were difficult to control, and required vaccine campaigns., Methods: Whole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates collected before and during the two outbreaks. We integrated and analyzed epidemiologic, geographic, and genomic data to better understand transmission networks among patients. Betweenness centrality was used as a metric to understand the most important geographic nodes in the transmission networks. Comparative genomics was used to identify genes associated with the outbreaks., Results: Neisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of isolates that were more distant from the outbreak strains, as well as those that should have been included based on high genomic similarity. Genomes for the second outbreak were more similar than the first and no polymorphism was found to either be unique or specific to either outbreak lineage. Betweenness centrality as applied to transmission networks based on phylogenetic analysis demonstrated that the outbreaks were transmitted within focal communities in NYC with few transmission events to other locations., Conclusions: Neisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help elucidate how it spreads geographically to facilitate targeted interventions to interrupt transmission., Competing Interests: All authors have no competing interests to declare. After the project data collection and analysis was completed, during the final phase of manuscript editing, D.A.J. was appointed to the board of the North Carolina Biotechnology Center. D.A.J. reaffirmed that he does not have any competing interests. The affiliation with DCS [A.T.L and P.A.R.] does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction and Objective: The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C., Materials and Methodology: The evolution of MD and by serogroup was analysed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analysed., Results: MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997-2000 to 15.44 per 100,000 in 2001-2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p<.01). Among those vaccinated, 66.4% of cases were serogroup B and 5.2% were C (p<.01). Mortality and case fatality rates were 7.7% and 0.19/100,000 respectively, without significant changes in time regarding case fatality., Conclusions: Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Background: Invasive meningococcal disease (IMD) is recognized as septicemia and/or meningitis. However, early symptoms may vary and are frequently nonspecific. Early abdominal presentations have been increasingly described. We aimed to explore a large cohort of patients with initial abdominal presentations for association with particular meningococcal strains., Methods: Confirmed IMD cases in France between 1991 and 2016 were screened for the presence within the 24 hours before diagnosis of at least 1 of the following criteria (1) abdominal pain, (2) gastroenteritis with diarrhea and vomiting, or (3) diarrhea only. Whole-genome sequencing was performed on all cultured isolates., Results: We identified 105 cases (median age, 19 years) of early abdominal presentations with a sharp increase since 2014. Early abdominal pain alone was the most frequent symptom (n = 67 [64%]), followed by gastroenteritis (n = 26 [25%]) and diarrhea alone (n = 12 [11%]). Twenty patients (20%) had abdominal surgery. A higher case fatality rate (24%) was observed in these cases compared to 10.4% in all IMD in France (P = .007) with high levels of inflammation markers in the blood. Isolates of group W were significantly more predominant in these cases compared to all IMD. Most of these isolates belonged to clonal complex 11 of the sublineages of the South American-UK strain., Conclusions: Abdominal presentations are frequently provoked by hyperinvasive isolates of meningococci. Delay in the management of these cases and the virulence of the isolates may explain the high fatality rate. Rapid recognition is a key element to improve their management.

Objectives: To describe the cluster of MenC ST11 Invasive Meningococcal Disease (IMD) occurred in Tuscany in the years 2015-2016., Methods: A retrospective charts analysis of clinical, epidemiological and microbiological aspects of documented IMD was performed. Prognostic factors for death were evaluated., Results: Sixty-one patients with IMD in the 2015-2016 period were documented: 28 had meningococcemia, 24 meningitis plus meningococcemia and 9 meningitis. MenC ST11 (cc11) was identified in 48/54 (89%) of the tested strains. All patients, with the exception of three very early death, received timely and appropriate antibiotic therapy and, in selected case, adjunctive therapy with steroids and Pentaglobin®. Forty-one patients recovered (67.3%, mean age: 26 years), 7 had permanent sequelae (11.3%, mean age 31 years) and 13 died (21.3%; mean age: 46 years). In a multivariate analysis, septic shock, purpura fulminans and advanced age were negative prognostic factors, while emergency admittance to a tertiary-care, university hospital, positively influenced the survival rate. The epidemiological analysis of the cluster identified close contacts and recreational environments such as discos as hotspot for MenC transmission. After a massive vaccination campaign, the number of MenC cases reported in Tuscany in 2017 decreased to 10, with no death., Conclusions: Vaccination campaign of key populations together with the need for rapid and qualified emergency care of the affected patients seems to be the main lesson learned by the MenC ST11 Tuscany epidemic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Data on purpura fulminans (PF) in adult patients are scarce and mainly limited to meningococcal infections. Our aim has been to report the clinical features and outcomes of adult patients admitted in the intensive care unit (ICU) for an infectious PF, as well as the predictive factors for limb amputation and mortality., Methods: A 17-year national multicenter retrospective cohort study in 55 ICUs in France from 2000 to 2016, including adult patients admitted for an infectious PF defined by a sudden and extensive purpura, together with the need for vasopressor support. Primary outcome variables included hospital mortality and amputation during the follow-up period (time between ICU admission and amputation, death or end of follow-up)., Results: Among the 306 included patients, 126 (41.2%; 95% CI 35.6-46.9) died and 180 (58.8%; 95% CI 53.3-64.3) survived during the follow-up period [13 (3-24) days], including 51/180 patients (28.3%, 95% CI 21.9-35.5) who eventually required limb amputations, with a median number of 3 (1-4) limbs amputated. The two predominantly identified microorganisms were Neisseria meningitidis (63.7%) and Streptococcus pneumoniae (21.9%). By multivariable Cox model, SAPS II [hazard-ratio (HR) = 1.03 (1.02-1.04); p < 0.001], lower leucocytes [HR 0.83 (0.69-0.99); p = 0.034] and platelet counts [HR 0.77 (0.60-0.91); p = 0.007], and arterial blood lactate levels [HR 2.71 (1.68-4.38); p < 0.001] were independently associated with hospital death, while a neck stiffness [HR 0.51 (0.28-0.92); p = 0.026] was a protective factor. Infection with Streptococcus pneumoniae [sub-hazard ratio 1.89 (1.06-3.38); p = 0.032], together with arterial lactate levels and ICU admission temperature, was independently associated with amputation by a competing risks analysis., Conclusion: Purpura fulminans carries a high mortality and morbidity. Pneumococcal PF leads to a higher risk of amputation., Trials Registration: NCT03216577.

Background: The case fatality rate (CFR) from invasive meningococcal disease (IMD) in New York City (NYC) is greater than national figures, with higher rates among females than males across all age groups., Methods: We conducted a retrospective cohort study among 151 persons aged ≥15 years diagnosed with IMD in NYC during 2008-2016 identified through communicable disease surveillance. We examined demographic, clinical, and community-level associations with death to confirm the elevated risk of mortality among female IMD patients after adjusting for confounders and to determine factors associated with female IMD mortality. Relative risks of death were estimated using multivariable log-linear Poisson regression with a robust error variance., Results: Females had a higher CFR (n = 23/62; 37%) following IMD than males (n = 17/89; 19%) (adjusted relative risk [aRR], 2.1; 95% confidence interval [CI], 1.2-3.8). Controlling for demographic and clinical factors, there was a significant interaction between sex and fatal outcomes related to meningitis: the relative risk of death for females with meningitis was 13.7 (95% CI, 3.2-58.1) compared with males. In the model restricted to females, altered mental status (aRR, 7.5; 95% CI, 2.9-19.6) was significantly associated with an increased risk of death., Conclusions: Female mortality from IMD was significantly increased compared with males, controlling for other predictors of mortality. Sex-based differences in recognition and treatment need to be evaluated in cases of meningococcal disease. Our study highlights the importance of analyzing routine surveillance data to identify and address disparities in disease incidence and outcomes.

Background: In 2013, the US Advisory Committee on Immunization Practices (ACIP) opted against adding meningococcal vaccines to the infant schedule due to poor cost-effectiveness. This raises a policy question: if meningococcal disease is too rare to justify routine vaccination, are there other vaccine-preventable causes of US infant deaths that could be supported?, Methods: We tabulated US infant deaths from 2009-2013 using the CDC WONDER database. These causes of death were then categorized into one of 3 categories: 1) vaccine-preventable using currently available interventions; 2) potentially vaccine-preventable within the next 10 years; and 3) not preventable., Results: From 19.8 million births (3.9 million/year), ∼122,000 infants died (0.62%). Of these, 181 (0.15% of all deaths) were preventable using currently available vaccines, while an additional 779 were categorized as potentially preventable in the next 10 y. By exclusion, 121,040 (99.2%) were judged 'not vaccine-preventable'. Meningococcal deaths contributed at most 0.03% of all infant deaths, but accounted for 17-34% of current vaccine-preventable deaths., Conclusions: The low number of vaccine-preventable deaths in the US makes it increasingly difficult to justify the introduction of any new infant vaccines.

Acute meningococcemia is characterized by extensive purpurae consisting of both petechiae and ecchymoses. This condition can be rapidly fatal without treatment due to shock and severe consumptive coagulopathy. We report a case of fatal meningococcal septicemia in a military recruit who presented with fever and associated rapidly progressive purpuric rash (purpura fulminans) without any meningeal signs. Evaluation revealed evidence of disseminated intravascular coagulopathy and multiorgan failure. Diplococci were demonstrated in peripheral blood neutrophils and monocytes. On autopsy, extensive hemorrhages were found in both adrenals, lungs, liver, skin, and kidneys with secondary hemophagocytic lymphohistiocytosis in bone marrow. This report highlights useful information obtained from examination of peripheral blood smear in purpura fulminans., Competing Interests: There are no conflicts of interest

Aim: To identify and describe potentially vaccine-preventable child deaths in New South Wales (NSW)., Methods: Child deaths in NSW from 2005 to 2014 potentially preventable by vaccination were identified from the NSW Child Death Register (maintained by the NSW Ombudsman) and the Notifiable Conditions Information Management System (NSW Health). Medical and post-mortem records were reviewed. Cases were classified as vaccine-preventable based on the strength of evidence for the relevant infection causing death and likelihood that death was preventable through vaccination. A two-source capture-recapture method was used to estimate the true number of deaths. Age-specific mortality rate and number of deaths by disease, area of residence and comorbidity were analysed. Deaths were classified as preventable based on vaccine availability, eligibility under the National Immunisation Program, age and presence of any contraindications., Results: Fifty-four deaths were identified as definitely or probably due to diseases for which a vaccine was available, with a total average annual mortality rate of 0.33 per 100 000 children and 2.1 per 100 000 infants. Two thirds of deaths occurred in children with no identified comorbidities. Twenty-three deaths were classified as preventable or potentially preventable by vaccination, with influenza (12 deaths) and meningococcal disease (five deaths) most common. An additional 15 deaths would be potentially preventable as of August 2016 due to immunisation recommendation changes including maternal vaccination., Conclusion: Maternal vaccination along with increased uptake of childhood influenza vaccination could reduce child deaths, particularly from influenza., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Neisseria meningitidis group W (NmW) belonging to the clonal complex ST-11 (NmW/cc11) spread in Europe and in France in 2000 and declined thereafter. In France, invasive meningococcal disease (IMD) due to NmW increased again in 2012 and thereafter since 2015. Several sub-lineages of NmW/cc11 are circulating worldwide with successive epidemic waves. We aimed to describe recent epidemiological trends of NmW in France and to explore the microbiological and epidemiological characteristics associated with different NmW/cc11 sub-lineages., Methods: The epidemiology of NmW was described based on data collected through mandatory notification of IMD and strain typing data for culture-confirmed and PCR-confirmed cases for the period 2000-2016. All culture-confirmed cases due to NmW from the period 2010-2016 were characterised by whole genome sequencing (WGS). A detailed epidemiological analysis was performed for culture-confirmed cases on the basis of WGS data., Findings: During the period 2010-2016, genotyping was obtained for 148 cases including all the 132 culture-confirmed cases, among which 127 were matched with epidemiological data, and 16 PCR-confirmed cases (out of a total of 47 PCR-confirmed cases). An increase in IMD was observed in 2012 and was linked to isolates belonging to the "Anglo-French-Hajj" sub-lineage. These isolates have decreased significantly since 2013 and have been replaced by NmW/cc11 isolates related to the "South American - UK" sub-lineage which caused a marked increase in the number of cases of NmW in 2016. In this sub-lineage, the "original UK strain" was first detected in 2012 and increased thereafter, followed by the recently described "UK 2013-strain". Isolates related to the "South American-UK" sub-lineage represented 45% of all NmW cultured isolates from the whole period 2010-2016 but were the most frequent isolates in 2016, representing 76% of the total NmW typed isolates and 94% of the typed NmW/cc11 isolates. A changing pattern in the epidemiology of NmW has been observed in 2015-2016 in relation to the spread of the "UK 2013-strain" with a sharp increase in the number of cases among persons aged 15 years and over and a high case fatality rate (CFR). Among cases due to the "UK 2013-strain", 94% of cases were aged 15 years and over and the CFR was 28%., Interpretation: Our data suggest a recent clonal replacement among NmW/cc11 isolates with the expansion of the "South American-UK" sub-lineage in France and particularly the "UK 2013-strain" which was predominant in 2015 and 2016. A shift in the age-distribution of IMD due to NmW to older ages and the high CFR are consistent with the expansion of a new virulent clone in a naive population. These data may have an impact on tailoring vaccination strategies against NmW., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis., Objectives: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease., Search Methods: We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017., Selection Criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach., Main Results: We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae., Authors' Conclusions: We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.

Objectives: This work aimed to describe the epidemiology of invasive meningococcal disease (IMD) in France, 2006-2015, including group- and genotype-specific disease burden, incidence trends before and after introduction of meningococcal C conjugate vaccines (MCCV) in 2010, and factors influencing the case fatality rate., Methods: Mandatory notification data on incidence and IMD case characteristics were used. Genotyping of invasive strains and whole genome sequencing were performed by the French National Reference Center. Vaccination coverage was estimated from the National Health Insurance Information System's reimbursement data., Results: The decrease in annual IMD incidence rates (per 100,000 inhabitants) from 1.23 in 2006 to 0.78 in 2016 was mainly related to the decrease in group B IMD. Group C incidence decreased from 0.29 in 2006 to 0.13 in 2010 but increased thereafter in age groups not targeted by MCCV. From 2010 onwards, MCCV coverage gradually increased but remained below 25% in 15-19 year-olds in 2015. Age, clinical presentation and, to a lesser extent, clonal complex 11 were the most significant factors determining mortality., Conclusions: The limited impact of vaccination on group C IMD incidence may be explained by the emergence of a new epidemic cycle in 2011 and the low vaccination coverage rates among adolescents and young adults., (Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Meningococcal disease (MD) is a medical emergency and a serious public health problem. As new meningococcal vaccines become available, MD surveillance is crucial to provide baseline epidemiologic data before implementing preventive measures. We estimated MD incidence and epidemiology in Argentina using hospital-based surveillance., Methods: Three-year prospective active surveillance in patients ≤15 years of age was conducted at 6 pediatric hospital sentinel units (March 2012 to February 2015)., Results: Of 184,360 hospitalized patients, 1444 (0.78%) had suspected meningitis or MD. Of these, 268 (19%) presented probable acute bacterial meningitis or MD, 168 (63%) were culture positive and 51 (30%) tested positive for Neisseria meningitidis. Of 100 culture-negative cases, 30 had positive meningococcal polymerase chain reaction. Thirteen patients presented other uncommon MD manifestations, resulting in a total of 94 MD cases and an annual incidence of 5.1/10 hospitalized patients [95% confidence interval (CI): 4-6]. Fifty-four (57%) patients were males, 48% were <1 year of age and the median age was 12.5 months (1 month to 15 years). Clinical presentations were the following: meningococcemia and meningitis (37%), meningitis (30%), meningococcemia (16%), arthritis (10%), bacteremia (5%) and pneumonia (2%). Twenty-eight percent had complications. Nine children died (case fatality rate: 10%), and 8 had sequelae. Serogroups were identified for 84 isolates. Serogroup W was associated with age <1 year (odds ratio: 3.18; 95% CI: 1.14-8.99); meningococcemia was associated with mortality (P = 0.0038)., Conclusions: Highest rates of MD were observed among young infants. This study provides baseline data to estimate the impact of introducing meningococcal vaccines in Argentina.

CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygous mice (CD46 +/+ ) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46 +/+ mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1β In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation. Additionally, CD46 +/+ macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46 +/+ peritoneal macrophages aggravated septic responses in wild-type mice, but the depletion of macrophages partially alleviated septic reactions in CD46 +/+ mice after N. meningitidis infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: In 1999, invasive meningococcal disease was hyperendemic in Ireland at 14.75/100 000 population, with 60% group B and 30% group C diseases. National sepsis guidelines and meningococcal C vaccines were introduced in 2000. Despite a spontaneous decline in group B infection, invasive meningococcal disease remains a leading cause of sepsis. This study characterises the epidemiology of invasive meningococcal disease in children in Ireland since the introduction of meningococcal C vaccine and reviews its clinical presentation, hospital course and outcome in anticipation of meningococcal B vaccine introduction., Methods: National surveillance data were obtained from the Health Protection Surveillance Centre. A retrospective study of all meningococcal cases at two tertiary paediatric hospitals was conducted from 2001 to 2011. Records were reviewed using a standardised assessment tool. A study of 407 meningococcal cases published in 2002 provided comparative data., Results: Of 1820 cases <19 years of age notified nationally, 382 (21%) cases attended a study hospital; 94% group B, 3% group C, 225 (59%) male, median age 5 years (range 0.1-18). Fever was absent at presentation in 18%. Fifteen patients (3.6%) died. 221 (61%) were admitted to paediatric intensive care units (PICU). Permanent sequelae occurred in 9.4%. Compared with the historical cohort, there were differences in presentation, an increase in PICU interventions, but no significant decline in morbidity or mortality., Conclusions: Despite the meningococcal C vaccination campaign, invasive meningococcal disease continues to cause serious morbidity and claim lives. Group B infections remain dominant. As children who die often present with fulminant disease, preventive strategies including use of meningococcal B vaccine are needed to avert death and sequelae., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Since 2000, when the meningococcal serogroupC conjugate vaccine (MenCC) was introduced in the childhood immunization schedule in Spain, several changes in the schedule and catch-up campaigns have been performed. We aim to estimate the impact and effectiveness of this vaccine in Navarra up to 2014., Methods: The impact of the vaccination program was analysed by comparing incidence, mortality and lethality rates of disease before (1995-1999) and after (2004-2014) the introduction of the MenCC. Vaccine effectiveness was estimated using the screening method (Farrington) and the indirect cohort method (Broome). Data on cases were obtained from the active surveillance of meningococcal disease., Results: During 1995-1999 the mean annual incidence of meningococcalC disease was 1.32 per 100,000, and 7.18 per 100,000 in children younger than 15years. The fall of meningococcalC disease incidence was significant in cohorts targeted for vaccination from the beginning and progressive in the general population. No cases were reported between 2011 and 2014. The estimated vaccine effectiveness was 96% by the screening method, and 99% by the indirect cohort method., Conclusion: The MenCC vaccination program has been successful in decreasing the incidence rate of serogroupC meningococcal disease in Navarra, and schedule changes have maintained high vaccine effectiveness throughout the study period., (Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Pneumonia is a public health problem in the tropics, and the 7-valent pneumococcal conjugative vaccine (PCV-7) has been introduced in an effort to prevent the disease and therefore reduce childhood mortality. In Rwanda, PCV-7 was introduced in 2009, and we aimed to determine its impact on the rate of child hospitalization/mortality due to pneumonia. A retrospective survey was conducted on hospitalization rates and pediatric deaths between two periods, that is, before the introduction of PCV-7 (2007-2009) and after the introduction of PCV-7 (2010-2013) in Kabutare District Hospital. There was a 53% reduction in hospitalization, with a significant decline in in-hospital deaths between the two periods. There was also a significant correlation between vaccination coverage and decline in hospitalization rates between 2009 and 2013. We conclude that PCV-7 vaccine is associated with significant reduction in the rate of child hospitalization and mortality but more mechanistic studies are warranted to determine the immunological impact, especially in the context of coinfections and malnutrition., (© The American Society of Tropical Medicine and Hygiene.)

Invasive meningococcal disease remains a substantial global public health burden despite being vaccine-preventable worldwide. More than one million cases are reported annually, with average fatality rates ranging from 10% to 40% depending on clinical presentation and geographic location. Survivors may suffer debilitating sequelae that reduce the quality of life for the patient and family members responsible for their care. Major financial burdens are associated with acute treatment and follow-up care, and outbreak management often places extensive financial strains on public health resources. Although the clinical and financial aspects of meningococcal disease burden are straightforward to quantify, other burdens such as lifelong cognitive deficits, psychological stress, adaptive measures for reintegration into society, familial impact, and legal costs are systematically overlooked. These and other facets of disease burden are therefore not systematically considered in cost-effectiveness analyses that public health authorities take into consideration when making decisions regarding vaccination programs. Changing the approach for measuring meningococcal disease burden is necessary to accurately understand the societal consequences of this devastating illness. In this article, the conventional and under-recognized burdens of meningococcal disease are presented and discussed., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

In England and Wales, meningococcal disease caused by group W has historically been associated with outbreaks of disease among travellers to high-risk countries. Following a large outbreak associated with travel to the Hajj in 2000, the number of cases declined and, in 2008, only 19 laboratory-confirmed cases were identified nationally. In 2013, in the East Midlands region of England, eight cases of meningococcal disease caused by this serogroup were recorded, compared with six from 2011 to 2012. To explore this further, data for all cases with a date of onset between 1 January 2011 and 31 December 2013 were collected. Data collected included geographical location, clinical presentation and outcome. Fourteen cases were identified; two died as a result of their illness and two developed long-term health problems. No commonality in terms of geographical location, shared space or activities was identified, suggesting that group W is circulating endemically with local transmission. Clinical presentation was variable. Half presented with symptoms not typical of a classical meningococcal disease, including two cases of cellulitis, which may have implications for clinicians, in terms of timely identification and treatment, and public health specialists, for offering timely antibiotic chemoprophylaxis to close contacts., (This article is copyright of The Authors, 2016.)

Background: To control an outbreak of invasive meningococcal disease (IMD) among men who have sex with men (MSM) in New York City, the New York City Department of Health and Mental Hygiene recommended vaccination of all HIV-infected MSM and at-risk HIV-uninfected MSM in October 2012., Methods: A decision-analytic model estimated the cost-effectiveness of meningococcal vaccination compared with no vaccination. Model inputs, including IMD incidence of 20.5 per 100,000 HIV-positive MSM (42% fatal) and 7.6 per 100,000 HIV-negative MSM (20% fatal), were from Department of Health and Mental Hygiene reported data and published sources. Outcomes included costs (2012 US dollars), IMD cases averted, IMD deaths averted, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs; $/QALY). Scenarios with and without herd immunity were considered, and sensitivity analyses were performed on key inputs., Results: Compared with no vaccination, the targeted vaccination campaign averted an estimated 2.7 IMD cases, 1.0 IMD deaths, with an ICER of $66,000/QALY when herd immunity was assumed. Without herd immunity, vaccination prevented 1.1 IMD cases, 0.4 IMD deaths, with an ICER of $177,000/QALY. In one-way sensitivity analyses, variables that exerted the greatest influence on results in order of effect were the magnitude of herd immunity, IMD case fatality ratio, and IMD incidence. In probabilistic sensitivity analyses, at a cost-effectiveness threshold of $100,000/QALY, vaccination was preferred in 97% of simulations with herd immunity and 20% of simulations without herd immunity., Conclusions: Vaccination during an IMD outbreak among MSM with and without HIV infection was projected to avert IMD cases and deaths and could be cost-effective depending on IMD incidence, case fatality, and herd immunity.

Background: Several countries consider the implementation of a meningococcal serogroup B vaccine for young children and/or serogroup C or ACWY conjugate vaccine for adolescents. Representative information on clinical course of invasive meningococcal disease (IMD) is useful to evaluate cost-effectiveness of vaccination. Information on the relation between infecting meningococcal clonal complex (CC), disease course and outcome of IMD is scarce., Methods: A retrospective study using Dutch surveillance data on IMD from June 1999 to June 2011. Clinical information was retrieved from hospital records. The effect of age, comorbidity, clinical manifestation, serogroup, and CC on disease course and outcome was assessed in multivariable analyses. Meningococcal CCs were assessed by multilocus sequence typing., Results: Clinical information was retrieved for 879 IMD cases: 48% of patients presented with meningitis, 17% with septic shock, and 22% with septic shock plus meningitis. Development of septic shock was not related to CC or serogroup. Median (interquartile range) duration of hospital admission was 10 (8-13) days. Intensive care unit admittance (38%) was higher for patients aged ≥10 years and patients with septic shock (P-values ≤.001). Case-fatality rate (8%) and development of sequelae (29%) was dependent on age and clinical manifestation (P-values ≤.001) and not affected by comorbidity, CC, or serogroup., Conclusions: IMD still coincides with a considerable disease burden and mortality. Disease course and outcome depend mainly on age and clinical manifestation and less on meningococcal CC or serogroup., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Meningococcal disease (MD) is a major global problem because of its case fatality rate and sequels. Since 2012 cases of serogroup W have increased in Chile, with nonspecific clinical presentation, high case fatality rate and serious consequences., Objective: To characterize the evolution and outcome of MD cases between January 2012 and March 2013 in Chile., Material and Methods: Case series considering 149 MD cases of 7 regions. A questionnaire was applied and clinical records were reviewed, including individual, agent, clinical course and healthcare process variables. The analysis allowed to obtain estimates of the OR as likelihood of dying., Results: 51.5% was meningococcemia, the case fatality rate reached 27%, prevailing serogroup W (46.6%). Factors that increased the probability of dying: > age, belonging to indigenous people, having lived a stressful event, having diarrhea, impaired consciousness, cardiovascular symptoms, low oxygen saturation and low Glasgow coma scale score., Discussion: The case fatality rate exceeded normal levels and was higher in serogroup W. Increasing in this serogroup, associated to the increased presence of nonspecific symptoms or rapid progression to septicemia, hit a health system accustomed to more classic meningococcal disease presentation, which could partly explain the observed increased fatality rate.

Background: Invasive meningococcal disease (IMD) is a major cause of bacterial meningitides and septicaemia. This study shows the results of the laboratory-based surveillance of IMD in Belgium over the period 1997-2012., Methods: The results are based on microbiological and molecular laboratory surveillance of 2997 clinical isolates of N. meningitides received by the Belgian Meningococcal Reference Centre (BMRC) over the period 1997-2012., Results: Serogroup B has always been a major cause of meningococcal disease in Belgium, with P3.4 as most frequent serotype till 2008, while an increase in non-serotypable strains has been observed in the last few years. Clonal complexes cc-41/44 and cc-269 are most frequently observed in serogroup B strains. In the late nineties, the incidence of serogroup C disease increased considerably and peaked in 2001, mainly associated with phenotypes C:2a:P1.5,2, C:2a:P1.5 and C:2a:P1.2 (ST-11/ET-37 clonal complex). The introduction of the meningococcal C conjugate vaccine has been followed by an 88% significant decrease in serogroup C disease from 2001 to 2004 nationally, yet sharper in Flanders (92%) compared to Wallonia (77%). Since 2008 a difference in incidence of serogroup C was observed in Flanders (0-0.1/100,000) versus Wallonia (0.1-0.3/100,000)., Conclusion: This study showed the change in epidemiology and strain population over a 16 years period spanning an exhaustive vaccination campaign and highlights the influence of regional vaccination policies with different cohorts sizes on short and long-term IMD incidences.

Meningococcal disease is a rare, rapidly progressing condition which may be difficult to diagnose, disproportionally affects children, and has high morbidity and mortality. Accurate incidence estimates are needed to monitor the effectiveness of vaccination and treatment. We used linked notification, hospital, mortality and birth data for all children of an Australian state (2000-2007) to estimate the incidence of meningococcal disease. A total of 595 cases were notified, 684 cases had a hospital diagnosis, and 26 cases died from meningococcal disease. All deaths were notified, but only 68% (466/684) of hospitalized cases. Of non-notified hospitalized cases with more than one clinical admission, most (90%, 103/114) did not have meningococcal disease recorded as their final diagnosis, consistent with initial 'false-positive' hospital meningococcal disease diagnosis. After adjusting for false-positive rates in hospital data, capture-recapture estimation suggested that up to four cases of meningococcal disease may not have been captured in either notification or hospital records. The estimated incidence of meningococcal disease in NSW-born and -resident children aged 0-14 years was 5·1-5·4 cases/100 000 child-years at risk, comparable to international estimates using similar methods, but lower than estimates based on hospital data.

Background: In England and Wales, the incidence of invasive meningococcal disease has been declining for more than a decade, but meningococcal group W (MenW) cases have been increasing since 2009., Methods: Public Health England conducts enhanced national surveillance of invasive meningococcal disease in England and Wales. Detailed clinical information was obtained for all laboratory-confirmed MenW cases diagnosed during 3 epidemiologic years (2010-2011 to 2012-2013), alongside whole-genome sequencing analysis of the clinical isolates., Results: The year-on-year increase in invasive MenW disease across all age groups since 2009-2010 was due to rapid endemic expansion of a single clone belonging to the sequence type 11 complex (cc11). In 2013-2014, MenW was responsible for 15% of all invasive meningococcal disease. All but 1 of the recent MenW:cc11 isolates were very closely related, consistent with recent clonal expansion. Clinical follow-up of all 129 MenW cases diagnosed during 2010-2011 to 2012-2013 revealed that most patients were previously healthy (n = 105 [81%]), had not travelled abroad prior to illness and the majority presented with septicemia (n = 63 [49%]), meningitis (n = 16 [12%]) or both (n = 21 [16%]); however, one-quarter had atypical presentations including pneumonia (n = 15 [12%]), septic arthritis (n = 9 [7%]), and epiglottitis/supraglottitis (n = 5 [4%]). Forty-eight (37%) required intensive care and 15 (12%) died. There was no association between infecting strain, clinical disease, or outcome., Conclusions: The recent increase in invasive MenW disease in England and Wales is due to rapid endemic expansion of a single clone belonging to cc11 and is associated with severe disease with unusual clinical presentations. This increase will require careful monitoring in the coming years., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to describe the magnitude, mortality, and case-fatality rate from meningococcal disease and to investigate predictors of death from this cause in the city of São Paulo, Brazil, from 1986 to 2004, using unconditional multiple logistic regression. We analyzed 10,087 cases of meningococcal disease in the city. Mean annual mortality was 1.0/100,000 inhabitants, ranging from 0.2 to 1.8. Case-fatality was 20.5%, with major differences according to age, serogroup, and type of hospital. Predictors of death from meningococcal disease were age, especially the age brackets from one to two years and 40 years and older, and serogroup W. The results can contribute to the elaboration of public policies with a focus on the organization of hospital care and protocols to promote greater treatment effectiveness and application of vaccination strategies that decrease the incidence in groups at greatest risk of death from meningococcal disease.

Introduction: The study aims to investigate the change in the burden of disease and the microbiological characteristics of Invasive Meningococcal Disease (IMD) in Puglia in comparison with overall incidence from 1994 through 2014., Methods: Data are gathered in the frame of the National Surveillance System coordinated by the National Reference Laboratory (NRL) of the Istituto Superiore di Sanità., Results: In Puglia, from 1994 through 2014, the average incidence of IMD was 0.2 per 100 000 inhabitants, below the national average value (0.33). IMD cases tended to be older than the other cases reported in Italy (median age 19 vs 16). The case-fatality rate was 20.4% in Puglia vs 13.3% in Italy. Serogroups B and C were most frequently identified. Serogroups C and Y presented a fairly clonal pattern, whereas serogroup B was genetically rather heterogeneous., Conclusion: Surveillance systems are critical in monitoring any change in the epidemiology of IMD.

Background: Before 2001, the incidence of invasive meningococcal disease (IMD) in Canada was 1.0 per 100 000 per year, with 40% of cases caused by serogroup C organisms. During 2001-2005 all provinces introduced the meningococcal serogroup C conjugate vaccine (MCCV) into their routine infant immunization schedule., Methods: Active, prospective, population-based surveillance of IMD in children and adults was conducted by the Canadian Immunization Monitoring Program, ACTive (IMPACT) during 2002-2012. Inclusion criteria were admission to hospital and identification of Neisseria meningitidis from a sterile site. Incidence was estimated using population census data from Statistics Canada., Results: Prior to MCCV introduction, serogroup C disease incidence was 0.07-0.25 per 100 000 per year depending on the province. Following vaccine introduction, serogroup C disease decreased to <0.05 per 100 000 per year, with a reduction of 14% per year (P = .0014). A decrease occurred in all provinces, despite differing schedules being implemented. The largest decrease of 83% (from 0.27 to 0.05 per 100 000 per year) occurred in the 15-24 year age group (P = .0100) who were not vaccinated in all provinces. There was no impact on the incidence of nonserogroup C disease over the same period (P = .9811)., Conclusions: MCCV dramatically reduced the incidence of serogroup C IMD in Canada through both direct and indirect effects. The observation that disease incidence decreased with different schedules suggests that the doses at 12 months (common to all provinces) and adolescence (7 of 8 provinces studied) were critical in achieving disease control., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)