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.

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.

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.

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.

Capsular switching in invasive Neisseria meningitidis, Brazil(1).

During the 1990s, an epidemic of B:4 Neisseria meningitidis infections affected Brazil. Subsequent increase in C:4 disease suggested B → C capsular switching. This study identified B → C switches within the sequence type 32 complex. Substantial disease related to capsular switching emphasizes the need for surveillance of circulating meningococcal strains to optimize disease control.

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.

Phenotypic and molecular characterization of serogroup C Neisseria meningitidis associated with an outbreak in Bahia, Brazil.

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. MATERIALS AND METHODS: The epidemiological investigation was conducted by the Epidemiological Surveillance Service of Bahia State. Meningococcal strains were characterized at Adolfo Lutz Institute, the Brazilian National Reference Laboratory for Bacterial Meningitis by conventional techniques (serotype, serosubtype and antimicrobial susceptibility test) and by molecular methods (Pulsed-field gel electrophoresis - PFGE and Multilocus Sequence Typing - MLST). RESULTS: The PFGE showed 2 closely related restriction profiles, designated as PFGE types A and A1, having 92% relatedness to each other. MLST characterization showed both A and A1 clones were ST-3780, which belongs to the ST-103 complex. All isolates displayed the phenotype C:23:P1.5 and were susceptible to all antibiotics tested. CONCLUSIONS: This is the first reported MD outbreak associated with serogroup C ST-103 complex in Brazil, as well as the party and illicit drug-use associated outbreak.

Surveillance for invasive meningococcal disease in children, US-Mexico border, 2005-2008.

We reviewed confirmed cases of pediatric invasive meningococcal disease in Tijuana, Mexico, and San Diego County, California, USA, during 2005-2008. The overall incidence and fatality rate observed in Tijuana were similar to those found in the US, and serogroup distribution suggests that most cases in Tijuana are vaccine preventable.

Proteome analysis of Neisseria meningitidis serogroup strains C associated with outbreaks in China.

OBJECTIVE: During 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed. METHODS: Clinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry. RESULTS: 502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426. CONCLUSIONS: The different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.

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.

Epidemiologic investigation and targeted vaccination initiative in response to an outbreak of meningococcal disease among illicit drug users in Brooklyn, New York.

BACKGROUND: An outbreak of serogroup C meningococcal disease that involved illicit drug users and their contacts occurred in Brooklyn, New York, during 2005 and 2006. METHODS: The objectives of this study were to identify the population at risk for meningococcal disease, describe efforts to interrupt disease transmission, and assess the impact of a vaccine initiative. Descriptive and molecular epidemiological analysis was used to define the extent of the outbreak and the common risk factors among outbreak-related cases. A vaccine initiative that used community-based service providers was targeted to illicit drug users and their close contacts. The vaccine initiative was assessed through cessation of outbreak-related cases and the reduction in carriage rate. RESULTS: The investigation identified 23 outbreak-related cases of serogroup C meningococcal disease; 17 isolates were indistinguishable and 4 isolates were closely related according to pulsed-field gel electrophoresis. Two additional culture-negative cases had epidemiological links to laboratory-confirmed cases. The median age of patients with outbreak-related cases was 41 years, and 19 (83%) of 23 patients reported an association with illicit drug use. There were 7 outbreak-related deaths. Vaccination was administered to 2763 persons at 29 community locations, including methadone treatment centers, syringe-exchange programs, and soup kitchens. Three additional cases of meningococcal disease due to strains with the same pulsed-field gel electrophoresis pattern were identified after the vaccination initiative. CONCLUSIONS: Community-based outbreaks of meningococcal disease are difficult to control, and the decision to vaccinate is not straightforward. Current national guidelines for implementing a vaccination campaign are not strict criteria and cannot be expected to accommodate the myriad of factors that occur in community-based invasive meningococcal disease outbreaks, such as the inability to enumerate the population at risk.

Serogroup C meningococci in Italy in the era of conjugate menC vaccination.

BACKGROUND: To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005-2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies. METHODS: IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), porA VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures. RESULTS: In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome. CONCLUSION: Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005-2007 National Vaccine Plan.

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.

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.

Identification of a new Neisseria meningitidis serogroup C clone from Anhui province, China.

BACKGROUND: Outbreaks of a new serogroup C meningococcal disease emerged during 2003-04 (five outbreaks with 43 cases) and in 2004-05 (five outbreaks with 29 cases), all in Anhui province, China. We describe the molecular epidemiology and features of the causative bacterial strains. METHODS: We used pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) to analyse the strains. FINDINGS: Of 34 strains of Neisseria meningitidis cultured during 2003-04 from Anhui province, 31 were group C meningococci, 28 of which were associated with three of five outbreaks; one from a patient and 27 from close contacts of eight patients. Of 30 strains isolated from Anhui province during 2004-05, 17 were identified as serogroup C meningococci, ten of which were associated with four of five outbreaks. In a nationwide survey, 542 strains were isolated during 2004-05; 58 were serogroup C meningococci interspersed among 11 other provinces where no serogroup C outbreak occurred. Of the 106 serogroup C strains analysed, 89 had identical PFGE patterns, designated AH1. Of 28 strains selected for MLST analyses, 25 were sequence type 4821 (ST-4821), which did not belong to any of the previously reported sequence types that can form a new hypervirulent lineage. INTERPRETATION: ST-4821 seems to be unique and caused the serogroup C meningitis outbreaks during the two seasons from 2003 to 2005 in Anhui province. The emergence of this sequence type has epidemiological importance that should be monitored for future spread in China and the rest of the world.