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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 analyzed 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 analyzed. 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 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.

INTRODUCTION In Tuscany, Italy, where a universal immunization program with monovalent meningococcal C conjugate vaccine (MCC) was introduced in 2005, an outbreak of invasive meningococcal disease (IMD) due to the hypervirulent strain of Neisseria meningitidis C/cc11 occurred in 2015-2016, leading to an immunization reactive campaign using either the tetravalent (ACWY) meningococcal conjugate or the MCC vaccine. During the outbreak, IMD serogroup C (MenC) cases were also reported among vaccinated individuals. This study aimed to characterize meningococcal C conjugate vaccines (MenC-vaccines) failures and to estimate their effectiveness since the introduction (2005-2016) and during the outbreak (2015-2016). METHODS MenC cases and related vaccine-failures were drawn from the National Surveillance System of Invasive Bacterial Disease (IBD) for the period 2006-2016. A retrospective cohort-study, including the Tuscany' population of the birth-cohorts 1994-2014, was carried out. Based on annual reports of vaccination, person-years of MenC-vaccines exposed and unexposed individuals were calculated by calendar-year, birth-cohort, and local health unit. Adjusted (by birth-cohort, local health unit, and calendar-year) risk-ratios (ARR) of MenC invasive disease for vaccinated vs unvaccinated were estimated by the Poisson model. Vaccine-effectiveness (VE) was estimated as: VE = 1-ARR. RESULTS In the period 2006-2016, 85 MenC-invasive disease cases were reported; 61 (71.8%) from 2015 to 2016. Twelve vaccine failures occurred, all of them during the outbreak. The time-interval from immunization to IMD onset was 20 days in one case, from 9 months to 3 years in six cases, and ≥7 years in five cases. VE was, 100% (95%CI not estimable, p = 0.03) before the outbreak (2006-2014) and 77% (95%CI 36-92, p

The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.

The glycoconjugate vaccines against Neisseria meningitidis are highly effective, however most of these vaccines are expensive and still out of reach in the developing world as well as the technical know-how and the set-up required for the consistent production of pure polysaccharide is limited. Our laboratory has developed rapid, efficient and scalable processes for the downstream purification of N. meningitidis serogroup A (MenA) and serogroup C (MenC) capsular polysaccharides (PS). The MenC-PS was purified with a novel 2-step procedure including de-O-acetylation and hydrophobic interaction chromatography whereas, MenA-PS was purified using a rapid method as compared to the prior art. The purified PSs were analyzed by various analytical tests including nuclear magnetic resonance, molecular weight, composition and purity analyses to meet desired specifications. Our results provide a proof of principle for the purification of MenA-PS and MenC-PS with reduced timelines.

Since the introduction of monovalent meningococcal serogroup C (MenC) glycoconjugate (MCC) vaccines and the implementation of national vaccination programmes, the incidence of MenC disease has declined markedly as a result of effective short-term vaccination and reduction in acquisition of MenC carriage leading to herd protection. Monovalent and quadrivalent conjugate vaccines are commonly used vaccines to provide protection against MenC disease worldwide. Studies have demonstrated that MCC vaccination confers protection in infancy (0-12 months) from the first dose but this is only short-term. NeisVac-C(®) has the greatest longevity of the currently licensed MCC vaccines in terms of antibody persistence, however antibody levels have been found to fall rapidly after early infant vaccination with two doses of all MCC vaccines - necessitating a booster at ∼12 months. In toddlers, only one dose of the MCC vaccine is required for routine immunization. If herd protection wanes following catch-up campaigns, many children may become vulnerable to infection. This has led many to question whether an adolescent booster is also required.

Objective To characterize meningococcal strains isolated from five cases of meningococcal disease (MD) associated with an outbreak in Trancoso – BA, occurred in October 2009. All cases, with the exception of a 39-year-old male, attended a dance party with approximately 1000 youngsters in a rural site.

Meningococcal C conjugate vaccine was introduced in the UK in November 1999 together with a comprehensive meningococcal surveillance strategy to support and inform the vaccine programme. These surveillance data have provided important information on the long-term effectiveness of the programme, through direct and indirect protection, and on the prevalent serotypes and serosubtypes causing invasive meningococcal infection subsequent to vaccine introduction. The MCC immunization programme has been extremely successful in controlling serogroup C disease and continues to be evaluated. The aim of this paper is to review the experiences in England and Wales over the past 9 years.

Purpose In Catalonia, a region in the northeast of Spain, a rate of five cases of meningococcal disease per 100,000 inhabitants was reported during the period of 1996–1997, which was higher than in previous years. The objective of this study was to analyze the temporal behavior of serogroup B and C meningococcal disease cases in Catalonia. Methods The study included confirmed cases of meningococcal disease from the 4-week period 11 of 1996 to the 4-week period 10 of 2004. A Poisson regression model (GLM) was fit for time series of serogroup B cases, whereas a zero-inflated Poisson model (ZIP) was necessary to adjust time series of serogroup C cases. Results The evolution of cases in both serogroups was correlated over time. For serogroup B, there was also an association with the influenza epidemics reported in four of the seasons analyzed. For serogroup C, a positive association with three influenza epidemics and a negative association with vaccination campaigns were found. Time series analysis of meningococcal disease shows that serogroups B and C behave in a different way. Conclusions The study of the evolution of each serogroup may be useful in evaluating vaccination strategies.

Meningococcal invasive disease is a life-threatening infection that affects mostly children and adolescents. The present study was performed during 2003–2005 to compare the phenotypic characteristics of meningococcal isolates from these two main groups at risk with those of isolates from other age groups to assess whether strategies for treatment and prevention implemented elsewhere can also be applied in Italy. The results showed that serogroup C meningococci were predominant, and that a dramatic increase in the circulation of strains with decreased susceptibility to penicillin was associated mainly with a prevalent phenotype C:2b:P1.5,2, which belongs to the hyper-virulent ST8/A4 cluster.

Different immunization strategies have been implemented for the control of serogroup C meningococcal disease (CMD) in Canada and in other developed countries. Results from effectiveness studies of conjugate vaccines in the UK and Spain indicate waning immunity over time. To estimate the life-time protection conferred by different immunization schedules, a simulation model was constructed based on the current epidemiologic situation in Canada. Results showed that the efficacy of any immunization schedule was highly influenced by the rate at which immunity waned and that the benefit of a booster dose increased with increasing rates of waning immunity. Schedules including several doses in early infancy provided little additional benefit over programs starting with 1 dose at the age of 12 months. One-dose programs provided low levels of protection, unless the vaccine was administered at the age of 12 months, and a waning immunity rate of 1% per year or less was assumed. The most effective schedule was 5 doses given at age 2 months, 4 months, 1 year, 12 years, and 18 years, but was only marginally better than 2 doses provided at 12 months and 12 years of age. Existing routine immunization schedules may not be optimal and should be designed to achieve the highest level of protection using the lowest number of doses.

Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae. The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135. Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children. Vaccines that protect against serogroup B disease are still in development. As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants. New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed. A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom. New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade. Copyright 2002, Elsevier Science (USA). All rights reserved.

The incidence of serogroup C meningococcal infection in the United Kingdom trebled during the 1990s; there was significant morbidity among age groups that were unresponsive to the available polysaccharide vaccines. The development, assessment, and deployment of meningococcal C conjugate vaccines was carried out in a program involving governmental health departments, public health agencies, and vaccine manufacturers. The effects of the program were assessed by an enhanced surveillance system. During the 1999/2000 season, the incidence of serogroup C infection had fallen significantly in vaccinated cohorts compared with previous years. The nationwide vaccination program is widely regarded as having been a public health success. Monitoring of the long-term impact of this intervention is in place.

Question How effective is the serogroup C conjugate meningococcal vaccine? Study design Before-after study, comparing infection rates before and after a mass immunisation programme after an epidemic; cohort analysis comparing infection rates in vaccinated and unvaccinated people 1 year after immunisation programme. Main results In the population aged between 2 months and 20 years (the immunisation target population), vaccine efficacy of the serogroup C oligosaccharide-CRM197 protein conjugate vaccine was 96.8% 1 year after vaccination (95% CI 75% to 99.9%; see notes). The incidence of serogroup C meningococcal infection in the immunisation target population, dropped from 21.47 per million people during the 2001 epidemic, to 3.26 per million in 2002, after the immunisation programme. Authors’ conclusions The serogroup C conjugate vaccine is highly effective for controlling epidemics of serogroup C meningococcal infection, and provides protection for at least 1 year.

www.thelancet.com Vol 383 January 18, 2014 217 efficacy, and safety of vaccine (in step 1), effect of the introduction of the vaccine in the immunisation programme and ethical aspects (in step 2)—have been assessed. Third, although the vaccines against meningococcal diseases serogroup B and serogroup C are completely diff erent, Martinon-Torres compares the epidemiological situation of both diseases at the time of authorisation of each vaccine and considers these similar. However, the evaluation done in September, 2000, showed an incidence rate for disease by serogroup C during the 1999– 2000 season of 1·01 per 100 000 (404 cases), whereas the incidence rate for disease by serogroup B in the 2011–12 season was about half of that: 0·52 per 100 000 (240 cases). In conclusion, we would like to emphasise that public health decisions regarding the inclusion of a vaccine into the National Immunisation Programme should be made not on emotional and rapid considerations, but only after an in-depth assessment of all epidemiological data and available information concerning the vaccine in the fi rst place; other criteria should be considered afterwards.

In most regards, the meningitis epidemic that struck Niger earlier this year was not unusual. It hit in March, the peak of the meningitis season, a period of dry weather and cold evenings ideal for transmission of the disease. The Ministry of Public Health recorded about 8500 cases, and 573 deaths up till June 28, 2015 a sizeable but not unprecedented outbreak—the 1996 epidemic killed roughly 12 000 people in neighbouring Nigeria. But the 1996 outbreak was caused by the group A meningococcus, historically responsible for more than 90% of epidemic meningitis in sub-Saharan Africa. The outbreak in Niger was caused by a new strain of meningitis C. Serogroup C had been thought only to be a serious problem in western Europe and the USA. Its involvement in an African epidemic has prompted WHO and partners including MSF and UNICEF to issue a joint warning that the continent must prepare for the possibility of a destructive outbreak over the 2016 meningitis season. The partners added that “an acute shortage of meningitis C containing vaccine threatens to severely limit the world’s ability to minimise the number of people aff ected”. Niger lies in the middle of the meningitis belt, which stretches from Senegal to Ethiopia, a region of roughly 300 million people. Niger is hyperendemic for the disease, and was one of the first countries to receive the Serum Institute’s meningococcal A conjugate vaccine after it began its rollout across the meningitis belt in 2010. More than 217 million people in sub-Saharan Africa have now been vaccinated against meningitis A; the continent has not seen a major outbreak of the disease since 2009. But the vaccine does not offer protection against meningitis C. For protection against the C serogroup, there are two options. The older polysaccharide vaccines only confer immunity for 2–3 years, and are not eff ective in very young children. Their production has dwindled since the advent of conjugate vaccines and they are now largely reserved for use in emergencies (more than 1 million doses were mobilised to combat the Niger outbreak). “The conjugate vaccines can be taken in infancy, off er a higher and better antibody response

Summary The UK was the first place to Introduce meningococcal serogroup C conjugate (MCC) vaccines. From November, 1999, all people younger than 18 years, about 14 million individuals, were offered MCC immunisation. The uptake rate was more than 70% by November, 2000. We compared the carriage of meningococci in isolates we obtained from 14 064 students aged 15–17 years during vaccination in 1999, with those from 16 583 students of the same age surveyed 1 year later. Carriage of serogroup C meningococci was reduced by 66% (p=0·004). Our results show that MCC vaccines protect against carriage of meningococci that express serogroup C polysaccharide capsules.

Summary A total of 110 strains of β-hemolytic streptococci, belonging to serogroup C ( Lancefield ), isolated from horses (71 S. zooepidemicus , 27 S. equisimilis and 12 S. equi ) as well as 5 reference strains were tested for their ability to produce hyaluronidase. The determinations were carried out in a culture test on agarose gel and in a liquid test system (turbidity test according to DiFerrante ). The results of both methods used showed that the three Streptococcus species could be differentiated by the relative quantitative determination of hyaluronidase activity. S. equisimilis strains produce 5 to 10 times more hyaluronidase than those of S. zooepidemicus . The strains of S. equi did not show enzyme production. In addition parallel tests by determination of final N-acetyl-D-glucosamine groups and by turbidity test were done to confirm the hyaluronidase activity of S. equisimilis strains. The comparison of results (Fig. 3) obtained from these tests, showed a good correspondence as demonstrated by a correlation index of 0,93.

Summary The plasmid content of twenty-nine Neisseria meningitidis strains, isolated from CSF and blood cultures, was investigated by agarose gel electrophoresis. The strains (twenty-seven from serogroup B and two from serogroup C) were sensitive to antibiotics, but 50% were resistant to sulphonamide (MIC≥16 mg/l). Two serogroup-B strains from CSF harboured an extrachromosomal element. These two cryptic plasmids differed in size: 8.4 Kb for pNMT1 and 82 Kb for pNMT2.