Gene flow and Bayesian phylogeography of serogroup C meningococci circulating in Italy.

INTRODUCTION: Hyperinvasive strains of Neisseria meningitidis serogroup C have caused outbreaks of severe disease in Italy. Here, we report the analysis of the migration patterns of C:P1.5-1,10-8:F3-6:ST-11(cc11) meningococcal strains from different Italian regions collected between 2012 and 2017. METHODS: N. meningitidis genomes were sequenced through the whole genome sequencing (WGS) method and were analyzed using the BIGSdb Genome Comparator tool. The phylogeography was performed using BEAST. The gene flows in Italy were tested by using MacClade. RESULTS: The C:P1.5-1,10-8:F3-6:ST-11(cc11) hyperinvasive meningococcal strain, for the data available at the time of the analysis, from UK reached at first Emilia Romagna region, and then, in 2012, was detected in the outbreak occurred in the port of Livorno. The "Tuscany-outbreak strain" was likely introduced in Italy between 2013 and 2014. Most of the observed gene flow events occurred from the Center to Northern part of Italy. DISCUSSION: The phylogeographic analysis allowed to track the dissemination of C:P1.5-1,10-8:F3-6:ST-11(cc11) strains in the country.

Molecular surveillance of brazilian meningococcal isolates serogroup c in the pre and post-men-c-vaccination period: Emergence of ST-3780.

Meningococcal disease is a devastating infection caused by Neisseria meningitidis (meningococcus), and it is classified into serogroups according to its polysaccharide capsule composition. In Brazil, serogroup C is the most frequently responsible for the majority of cases, representing a serious public health challenge. In 2010, the meningococcal serogroup C conjugate vaccine was included in the calendar of the National Immunization Program. We have evaluated 163 meningococcal isolates collected during the pre (2006-2010) and post (2011-2016) vaccination periods. Epidemiological data were determined through Multilocus Sequence Typing (MLST) analysis, vaccine antigens and Bexsero Antigen Sequence Typing (BAST) variant. Clonal complex 103 remains the most prevalent in the country with a high number of serogroup C strains to which CC103 is directly associated. A total of 42 different ST were found. The two most prevalent ST were ST-3780 (CC103) with 38 strains and ST-10781, which was not associated with a CC with nine strains. Allele abcZ-276 was reported among 98% of the strains analyzed and it was not found among other CC103 strains worldwide, makes this allele an important genetic marker for a specific new clone only assigned to Brazilian serogroup C strains, ST-3780. FHbp-25 and NHBA-42 peptides were the most prevalent among isolates in both periods studied. BAST-824 and BAST-3073 have been expressed only in CC103 over the studied years, however, it was not possible to associate a BAST variant to a specific CC. Serogroup C phenotype [P1.22,14-6,36-2: F3-9: ST-3780 (CC103)] was the most prevalent according to the antigenic profiles of circulating strains in Brazil (2007-2016). Our study suggests that CC103 is still a major hypervirulent CC circulating in Brazil and ST-3780 is currently spreading all over the country even after the introduction of MenC in 2010.

A New Sequence Type of Neisseria meningitidis Serogroup C Associated With a 2016 Meningitis Outbreak in Mali.

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouéléssebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

Spatiotemporal Analysis of Serogroup C Meningococcal Meningitis Spread in Niger and Nigeria and Implications for Epidemic Response.

BACKGROUND: After the re-emergence of serogroup C meningococcal meningitis (MM) in Nigeria and Niger, we aimed to re-evaluate the vaccination policy used to respond to outbreaks of MM in the African meningitis belt by investigating alternative strategies using a lower incidence threshold and information about neighboring districts. METHODS: We used data on suspected and laboratory-confirmed cases in Niger and Nigeria from 2013 to 2017. We calculated global and local Moran's I-statistics to identify spatial clustering of districts with high MM incidence. We used a Pinner model to estimate the impact of vaccination campaigns occurring between 2015 and 2017 and to evaluate the impact of 3 alternative district-level vaccination strategies, compared with that currently used. RESULTS: We found significant clustering of high incidence districts in every year, with local clusters around Tambuwal, Nigeria in 2013 and 2014, Niamey, Niger in 2016, and in Sokoto and Zamfara States in Nigeria in 2017.We estimate that the vaccination campaigns implemented in 2015, 2016, and 2017 prevented 6% of MM cases. Using the current strategy but with high coverage (85%) and timely distribution (4 weeks), these campaigns could have prevented 10% of cases. This strategy required the fewest doses of vaccine to prevent a case. None of the alternative strategies we evaluated were more efficient, but they would have prevented the occurrence of more cases overall. CONCLUSIONS: Although we observed significant spatial clustering in MM in Nigeria and Niger between 2013 and 2017, there is no strong evidence to support a change in methods for epidemic response in terms of lowering the intervention threshold or targeting neighboring districts for reactive vaccination.

Pediatric Bacterial Meningitis Surveillance in Niger: Increased Importance of Neisseria meningitidis Serogroup C, and a Decrease in Streptococcus pneumoniae Following 13-Valent Pneumococcal Conjugate Vaccine Introduction.

BACKGROUND: Meningitis is endemic in Niger. Haemophilus influenzae type b (Hib) vaccine and the 13-valent pneumococcal conjugate vaccine (PCV13) were introduced in 2008 and 2014, respectively. Vaccination campaign against Neisseria meningitidis serogroup A was carried out in 2010-2011. We evaluated changes in pathogen distribution using data from hospital-based surveillance in Niger from 2010 through 2016. METHODS: Cerebrospinal fluid (CSF) specimens from children <5 years old with suspected meningitis were tested to detect vaccine-preventable bacterial pathogens. Confirmatory identification and serotyping/grouping of Streptococcus pneumoniae, N. meningitidis, and H. influenzae were done. Antimicrobial susceptibility testing and whole genome sequencing were performed on S. pneumoniae isolates. RESULTS: The surveillance included 2580 patients with suspected meningitis, of whom 80.8% (2085/2580) had CSF collected. Bacterial meningitis was confirmed in 273 patients: 48% (131/273) was N. meningitidis, 45% (123/273) S. pneumoniae, and 7% (19/273) H. influenzae. Streptococcus pneumoniae meningitis decreased from 34 in 2014, to 16 in 2016. PCV13 serotypes made up 88% (7/8) of S. pneumoniae meningitis prevaccination and 20% (5/20) postvaccination. Neisseria meningitidis serogroup C (NmC) was responsible for 59% (10/17) of serogrouped N. meningitidis meningitis. Hib caused 67% (2/3) of the H. influenzae meningitis isolates serotyped. Penicillin resistance was found in 16% (4/25) of S. pneumoniae isolates. Sequence type 217 was the most common lineage among S. pneumoniae isolates. CONCLUSIONS: Neisseria meningitidis and S. pneumoniae remain important causes of meningitis in children in Niger. The decline in the numbers of S. pneumoniae meningitis post-PCV13 is encouraging and should continue to be monitored. NmC is the predominant serogroup causing N. meningitidis meningitis.

Carriage rates and risk factors during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11) in Tuscany, Italy: a cross-sectional study.

BACKGROUND: During 2015-2016 an outbreak of invasive meningococcal disease due to N. meningitidis serogroup C ST-11 (cc11) occurred in Tuscany, Italy. The outbreak affected mainly the age group 20-30 years, men who have sex with men, and the area located between the cities of Firenze, Prato and Empoli, with discos and gay-venues associated-clusters. A cross-sectional-survey was conducted to assess the prevalence and risk factors for meningococcal-carriage, in order to address public health interventions. METHODS: A convenience sample of people aged 11-45 years provided oropharyngeal swab specimens and completed questionnaires on risk factors for meningococcal carriage during a 3 months study-period, conducted either in the outbreak-area and in a control-area not affected by the outbreak (cities of Grosseto and Siena). Isolates were tested by culture plus polymerase chain reaction. Serogroup C meningococcal isolates were further characterized using multilocus sequence typing. Univariate and multivariate analyses were performed to estimate adjusted odds ratios (AORs) for meningococcal carriage. RESULTS: A total of 2285 oropharyngeal samples were collected. Overall, meningococcal carriage prevalence was 4.8% (n = 110), with nonencapsulated meningococci most prevalent (2.3%; n = 52). Among encapsulated meningococci, serogroup B was the most prevalent (1.8%; n = 41), followed by serogroup Y (0.5%; n = 11) and serogroup C (0.2%; n = 4); one carrier of serogroup E and one of serogroup Z, were also found (0.04%). Three individuals from the city of Empoli were found to carry the outbreak strain, C:ST-11 (cc11); this city also had the highest serogroup C carriage prevalence (0.5%). At the multivariate analyses, risk factors for meningococcal carriage were: illicit-drugs consumption (AOR 6.30; p < 0.01), active smoking (AOR 2.78; p = 0.01), disco/clubs/parties attendance (AOR 2.06; p = 0.04), being aged 20-30 years (AOR 3.08; p < 0.01), and have had same-sex intercourses (AOR 6.69; p < 0.01). CONCLUSIONS: A low prevalence of meningococcal serogroup C carriage in an area affected by an outbreak due to the hypervirulent N. meningitidis serogroup C ST-11 (cc11) strain was found. The city of Empoli had the highest attack-rate during the outbreak and also the highest meningococcal serogroup C carriage-prevalence due to the outbreak-strain. Multivariate analyses underlined a convergence of risk factors, which partially confirmed those observed among meningococcal outbreak-cases, and that should be considered in targeted immunization campaigns.

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

BACKGROUND: On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. METHODS: We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. FINDINGS: 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. INTERPRETATION: This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. FUNDING: US Global Health Security.

Dissemination of the ST-103 clonal complex serogroup C meningococci in Salvador, Brazil.

Invasive meningococcal disease (IMD) is a major public health problem worldwide. An epidemic of serogroup C (NmC) IMD occurred in 2010 in the city of Salvador. In this study, we describe the antigenic and genetic characterization of meningococcal isolates collected from meningitis cases in Salvador from 2001 to 2012. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed for the analysis of IMD isolates. A total of 733 cases were identified, and the serogroup was determined for 391 (53.0%) of these. Most cases were caused by NmC (53%) or B (47%). The most prevalent strains were B:4,7:P1.19,15 (32.9%; 129/391) and C:23:P1.14-6 (28.6%; 112/391). Based on PFGE/MLST analysis, 71.3% (77/108 PFGE-tested isolates) clustered as two clones of sequence type ST-3779 and ST-3780, both belonging to the ST-103 clonal complex. ST-3779 has been detected in Salvador since 1996 and together with ST-3780 became predominant after 2005. There was a predominance of C:23:P1.14-6, ST-3779/3780 in Salvador during the period of 2007-2012, establishing a major clonal lineage, which remained in the community for a long time; this has serious implications for public health, particularly in terms of prevention and control strategies of IMD.

Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men.

Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.

Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11.

OBJECTIVES: To describe a spatio-temporal cluster of invasive meningococcal disease (IMD) due to serogroup C meningococci, occurred in a restricted area of Tuscany between January and October 2015, and the results of whole genome sequencing (WGS). METHODS: Surveillance activities and public health measures were implemented in the Region. Bacterial isolates from IMD cases were characterized by the National Reference Laboratory of the Istituto Superiore di Sanità (ISS), and WGS was performed on available strains. The kSNP software was used to identify core genome SNPs. RESULTS: Overall, 28 IMD cases due to meningococcus C were identified up to 31st October, 2015. Of them, 26 were due to meningococcus C:P1.5-1,10-8: F3-6:ST-11 (cc11) and 2 to C:P1.5-1,10-8: F3-6:ST-2780 (cc11). WGS of 13 meningococci isolated during the outbreak occurred in Tuscany in 2015 showed higher similarity when compared with those of 47 C: P1.5-1,10-8: F3-6:ST-11 (cc11) invasive strains from sporadic cases previously detected in Italy. CONCLUSIONS: A highly aggressive meningococcal C strain was involved in the cluster of severe IMD occurred in Tuscany, a Region with high vaccine coverage among children. Whether this was due to low herd immunity related to the short duration of vaccine protection needs further investigation.

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage.

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.

Changes in Meningococcal Strains in the Era of a Serogroup C Vaccination Campaign: Trends and Evolution in Belgium during the Period 1997-2012.

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.

Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage.

OBJECTIVES: Neisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000-2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution. METHODS: Representatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks. RESULTS: MenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the 'Hajj outbreak' strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct. CONCLUSIONS: High resolution 'genomic' multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally.

Multilocus variable-number tandem-repeat analysis of Neisseria meningitidis serogroup C in China.

This study characterized Neisseria meningitidis serogroup C strains in China in order to establish their genetic relatedness and describe the use of multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) to provide useful epidemiological information. A total of 215 N. meningitidis serogroup C strains, obtained from 2003 to 2012 in China, were characterized by MLVA with different published schemes as well as multilocus sequence typing. (i) Based on the MLVA scheme with a combination of five highly variable loci, 203 genotypes were identified; this level of discrimination supports its use for resolving closely related isolates. (ii) Based on a combination of ten low variable loci, clear phylogenetic relationships were established within sequence type complexes. In addition, there was evidence of microevolution of VNTR loci over the decade as strain lineages spread from Anhui to other provinces, the more distant the provinces from Anhui, the higher the genetic variation.

Genetic and antigenic characterization of Canadian invasive Neisseria meningitidis serogroup C (MenC) case isolates in the post-MenC conjugate vaccine era, 2009-2013.

We previously reported a shift in the electrophoretic type (ET) of invasive MenC in Canada from predominantly ET-15 to ET-37 in the post-MenC conjugate vaccine period. This study sought to confirm this trend by examining all culture-confirmed invasive MenC case isolates in Canada in the period from 1 January 2009 to 31 December 2013. Of the 50 MenC isolates, 18 belonged to ET-15, 28 belonged to ET-37 (but not ET-15), and four belonged to other clonal types. Analysis of the serotype and serosubtype antigens, porA and fetA gene sequences provided data to show that invasive MenC belonging to ET-15 and ET-37 were two very different subpopulations within the ST-11 clonal complex. Sequence analysis of the fHbp genes suggested that 12 different types of factor H-binding protein were found among the ET-15 isolates while 86 % of ET-37 isolates were found to have fHbp genes predicted to encode peptide 22. The nadA gene in 12 MenC isolates was disrupted due to IS1301 insertion and 11 of these 12 isolates belonged to ET-15. Ten per cent of the invasive MenC were found to have a frame-shift mutation in their fHbp genes that predicted no fHbp produced. Significant diversity and frame-shift mutations of fHbp genes were found in invasive MenC strains in Canada.

Genetic diversity of Neisseria meningitidis serogroup C ST-4821 in China based on multiple-locus variable number tandem repeat analysis.

Neisseria meningitidis sequence type (ST)-4821 was first reported in China in 2003, and a new hyper-virulent lineage has been designated as the ST-4821 complex. A large number of N. meningitidis ST-4821 strains have been identified in China since 2003; however, the microevolution characteristics of this complex are unclear. Different combinations of variable number of tandem repeats (VNTR) loci were used in multiple-locus VNTR analysis (MLVA) to analyze 118 N. meningitidis serogroup C ST-4821 strains isolated from seventeen provinces between 2003 and 2012. Additionally, MLVA with five VNTR loci was performed due to its high discriminatory power. One hundred and eighteen isolates were found to comprise 112 subtypes based on MLVA, and 16 outbreak-associated strains were clustered into one group. These data indicate a high level of diversity for N. meningitidis ST-4821 due to microevolution in the last decade. In addition, the results revealed high similarity between isolates from the same geographic origins, which is helpful when monitoring the spread of N. meningitidis serogroup C ST-4821 and will provide valuable information for the control and prevention of bacterial meningitis in China.

A decade of herd protection after introduction of meningococcal serogroup C conjugate vaccination.

BACKGROUND: Vaccination with meningococcal serogroup C (MenC) conjugate (MCC) polysaccharide vaccines led to a substantial decline in MenC disease in the vaccinated and the unvaccinated population. The decline in the unvaccinated population can be explained by herd protection by reduced colonization of meningococci expressing the MenC capsule. The duration of such herd protection is unknown. METHODS: In a nationwide study from the Netherlands, we compared MenC invasive disease between 1998 and the introduction of MCC vaccination (2002) with that from 2002 to 2012, in age groups eligible and not eligible for vaccination. The proportions of isolates from clonal complexes with high serogroup C capsule expression rate during carriage (sequence type [ST] 11 and ST-8 complex) was compared between the pre- and postvaccination periods. RESULTS: A total of 814 patients with invasive MenC disease were included for analysis. There was a 99% decline in MenC disease in patients eligible for vaccination and a 93% decline in those not eligible. Thirty-six percent of the overall MenC reduction between the first and last 4 years of the observation period occurred in the unvaccinated population. Clonal complex was determined in 350 (43%) isolates. The proportion of cases caused by clonal complex ST-11 and ST-8 serogroup C meningococci decreased from 251 of 268 (94%) before, to 46 of 57 (81%) after MCC vaccine introduction (P = .004). CONCLUSIONS: Our findings provide further evidence that herd protection results from reduced carriage of virulent meningococci. Herd protection was responsible for >36% of MCC vaccine impact and lasted for ≥10 years.

Three outbreak-causing Neisseria meningitidis serogroup C clones, Brazil(1.).

During 2003-2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates.

Replacement of Neisseria meningitidis C cc11/ET-15 variant by a cc103 hypervirulent clone, Brazil 2005-2011.

Outbreaks caused by serogroup C meningococci in the northeast region of Brazil from 2005 to 2011 were associated to the emergence of variant ET-15 of cc11, which has been replaced by cc103 from 2006 to date. The increase of cc103 should be closely monitored to prevent the spread of this clone to neighbouring regions.

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China.

BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15-24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.