Genome-Based Characterization of Emergent Invasive Neisseria meningitidis Serogroup Y Isolates in Sweden from 1995 to 2012.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y has increased in Europe, especially in Scandinavia. In Sweden, serogroup Y is now the dominating serogroup, and in 2012, the serogroup Y disease incidence was 0.46/100,000 population. We previously showed that a strain type belonging to sequence type 23 was responsible for the increased prevalence of this serogroup in Sweden. The objective of this study was to investigate the serogroup Y emergence by whole-genome sequencing and compare the meningococcal population structure of Swedish invasive serogroup Y strains to those of other countries with different IMD incidence. Whole-genome sequencing was performed on invasive serogroup Y isolates from 1995 to 2012 in Sweden (n = 186). These isolates were compared to a collection of serogroup Y isolates from England, Wales, and Northern Ireland from 2010 to 2012 (n = 143), which had relatively low serogroup Y incidence, and two isolates obtained in 1999 in the United States, where serogroup Y remains one of the major causes of IMD. The meningococcal population structures were similar in the investigated regions; however, different strain types were prevalent in each geographic region. A number of genes known or hypothesized to have an impact on meningococcal virulence were shown to be associated with different strain types and subtypes. The reasons for the IMD increase are multifactorial and are influenced by increased virulence, host adaptive immunity, and transmission. Future genome-wide association studies are needed to reveal additional genes associated with serogroup Y meningococcal disease, and this work would benefit from a complete serogroup Y meningococcal reference genome.

Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013.

In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p < 0.001). Overall 81 serogroup Y IMD cases were identified, with a median age of 18 years, ranging from three months to 84 years. Of the 81 respective patient samples, 56 were further subject to molecular typing. The sequence type (ST)-23 complex (clonal complex (cc)23) was predominant among serogroup Y meningococci (54/56 samples), and included nine different STs. Presumably, ST-23 was the founding genotype, with all the other STs presenting as single-locus variants. All cc23 isolates analysed harboured mutations in the lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.

Temporal variations in the serogroup distribution of invasive meningococcal disease in Quebec, Canada, due to emerging unique clade of serogroup Y strain belonging to the Sequence Type-23 clonal complex.

OBJECTIVE: To identify recent trends in invasive meningococcal diseases (IMD) in Quebec, Canada, with a focus on MenY cases and MenY strains. METHODS: IMD cases and MenY strains from January 1, 2015 to August 11, 2023 were analyzed for clonal analysis and prediction of susceptibility to MenB vaccines. MenY strains of ST-23 CC from Quebec were analyzed with global MenY strains by core-genomic multi-locus sequence typing (cg-MLST). RESULTS: Since 2015 the serogroup distribution of IMD in Quebec has shifted from predominantly MenB to mainly MenY, with most (80.9 %) of the latter belonging to ST-23 CC. The median age of MenY cases due to ST-23 CC were statistically younger than MenY cases due to non-ST-23 CC. MenY of ST-23 CC showed genetic diversity and the major genetic cluster were similar to the Swedish Y1 strain. The increase in invasive MenY disease in Quebec was due to a sub-clade of Lineage 23.1 which caused an elevated proportion of severe disease in young adults. CONCLUSION: The increase in invasive MenY disease in Quebec, Canada was driven by the expansion of a sub-clade of Lineage 23.1 in young adults. Currently available quadrivalent A,C,W,Y-conjugate meningococcal vaccines were predicted to provide protection against these strains.

Invasive meningococcal capsular group Y disease, England and Wales, 2007-2009.

Enhanced national surveillance for invasive meningococcal disease in England and Wales identified an increase in laboratory-confirmed capsular group Y (MenY) disease from 34 cases in 2007 to 44 in 2008 and 65 in 2009. For cases diagnosed in 2009, patient median age at disease onset was 60 years; 39% of patients had underlying medical conditions, and 19% died. MenY isolates causing invasive disease during 2007-2009 belonged mainly to 1 of 4 clonal complexes (cc), cc23 (56% of isolates), cc174 (21%), cc167 (11%), and cc22 (8%). The 2009 increase resulted primarily from sequence type 1655 (cc23) (22 cases in 2009, compared with 4 cases each in 2007 and 2008). cc23 was associated with lpxL1 mutations and meningitis in younger age groups (<25 years); cc174 was associated with nonmeningitis, particularly pneumonia, in older age groups (>65 years). The increase in MenY disease requires careful epidemiologic and molecular monitoring.

Fatal Waterhouse-Friderichsen syndrome in an adult due to serogroup Y Neisseria meningitidis.

Waterhouse-Friderichsen syndrome (WFS), defined as severe adrenal insufficiency due to bilateral adrenal gland haemorrhagic necrosis, occurred in a 59-year-old woman. An underlying serogroup Y Neisseria meningitidis (NM) infection was diagnosed, with a rapid progression to purpura fulminans, disseminated intravascular coagulation and WFS. Intensive treatment including fluid resuscitation, broad-spectrum antibiotic therapy, ventilatory support, platelet and factor replacement were administered. The meningococcaemia in the presence of WFS had a fulminant progression, leading to a fatal outcome within 24 hours of symptom onset. This case details the diagnosis and management challenges of the WFS, a rare complication of NM septicaemia, and describes the identification of a NM serogroup that is rare in Portugal in middle-aged patients.

Genotypic comparison of invasive Neisseria meningitidis serogroup Y isolates from the United States, South Africa, and Israel, isolated from 1999 through 2002.

The proportion of meningococcal disease in the United States, South Africa, and Israel caused by Neisseria meningitidis serogroup Y (NmY) was greater than the worldwide average during the period 1999-2002. Genotypic characterization of 300 NmY isolates by multilocus sequence typing, 16S rRNA gene sequencing, and PorA variable region typing was conducted to determine the relationships of the isolates from these three countries. Seventy different genotypes were found. Two groups of ST-23 clonal complex isolates accounted for 88% of the U.S. isolates, 12% of the South African isolates, and 96% of the isolates from Israel. The single common clone (ST-23/16S-19/P1.5-2,10-1) represented 57, 5, and 35% of the NmY isolates from the United States, South Africa, and Israel. The predominant clone in South Africa (ST-175/16S-21/P1.5-1,2-2), and 11 other closely related clones made up 77% of the South African study isolates and were not found among the isolates from the United States or Israel. ST-175 was the predicted founder of the ST-175 clonal complex, and isolates of ST-175 and related sequence types have been described previously in other African countries. Continued active surveillance and genetic characterization of NmY isolates causing disease in the United States, South Africa, and Israel will provide valuable data for local and global epidemiology and allow monitoring for any expansion of existing clonal complexes and detection of the emergence of new virulent clones in the population.

Serological and genetic characterization of meningococcal isolates in Korea.

Meningococcal disease has been regarded as a very rare infection in Korea. Until now, there have been no reports on the serological or genetic characterization of Neisseria meningitidis isolates in Korea. This study was the first report of the serogroup, PorA VR subtype, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and antimicrobial susceptibility of N. meningitidis isolates collected from 2002 to 2003. Of 11 meningococcal isolates, serogroup Y was found to be the most frequent (nine isolates). In addition, one isolate was from serogroup B and one was from serogroup 29E. Four isolates showed a reduced sensitivity to penicillin G. However, all strains tested were susceptible to chloramphenicol, cefotaxime, ciprofloxacin, and rifampin. Among the 11 isolates, seven PorA types were identified. P1.5-1, 2-2 was the most prevalent PorA type, accounting for 55.6% of the serogroup Y isolates. In terms of PFGE patterns, nine isolates of serogroup Y were divided into three clusters, but the isolates shared a high level of PFGE pattern similarity. The serogroup Y isolates were characterized as ST-1625 (five strains) and ST-23 (four). They belonged to the ST-23 complex/Cluster A3. In this study, the ST-23 complex/Cluster A3 was prevalent, with the PorA type P1.5-1, 2-2 accounting for 55.6% of the nine serogroup Y strains. Also, we identified the hypervirulent lineage strain such as ST-6667 of ST-41/44 complex/Lineage 3 in Korea. The results of this study show the need for comprehensive epidemiological surveillance to monitor any changes in the meningococcal disease situation so that prompt intervention can be initiated.

Fulminant invasive meningococcal disease due to serogroup Y infection: a highly unusual case reflecting worrying increases in carriage and incidence.

A young man presented to accident and emergency with a short history of diarrhoea and vomiting, with no medical history. He deteriorated rapidly during triage and never regained consciousness. He was pronounced dead after hours of attempted resuscitation. He was found to have organisms suggestive of diplococci on his blood film and subsequently had MenY found via PCR testing. This case illustrates a highly unusual presentation of invasive meningococcal disease caused by MenY which is quietly and dangerously increasing in incidence in the UK, particularly in young healthy patients. All clinicians are reminded to be vigilant in order to diagnose and treat this often fatal disease as well as to promote uptake of the quadrivalent MenACWY vaccine.

First description of a rifampicin-resistant Neisseria meningitidis serogroup Y strain causing recurrent invasive meningococcal disease in Hungary.

A Hungarian soldier previously immunized against Neisseria meningitidis by quadrivalent polysaccharide vaccine was twice infected with meningococci within six weeks. The patient was treated with ceftriaxone during both episodes and he successfully recovered. His close contacts received rifampicin prophylaxis. An investigation was performed to characterize the genetic background of the pathogens to ascertain if the recurrent invasive meningococcal disease was caused by the same strain and to find out the reason for reinfection. Both meningococci belonged to the fine type Y:P1.5-2,10-1:F4-1:ST-23. This is the first description of the Europe-wide prevalent N. meningitidis serogroup Y in Hungary. In the first episode, we found wild-type rpoB allele in the non-culturable sample implying the susceptibility to rifampicin. The culturable isolate from the second episode proved resistant to rifampicin and had a point mutation in the rpoB gene. The rifampicin resistance might have evolved during the prophylactic treatment of contacts. Previous immunization of the patient with polysaccharide vaccine was ineffective due to his immunodeficiency, thus immunization with conjugate vaccine was proposed. We have proposed the implementation of centralized rifampicin susceptibility testing of N. meningitidis strains within a defined time frame to intervene and administer appropriate prophylaxis to close contacts.

New rapid diagnostic tests for Neisseria meningitidis serogroups A, W135, C, and Y.

BACKGROUND: Outbreaks of meningococcal meningitis (meningitis caused by Neisseria meningitidis) are a major public health concern in the African "meningitis belt," which includes 21 countries from Senegal to Ethiopia. Of the several species that can cause meningitis, N. meningitidis is the most important cause of epidemics in this region. In choosing the appropriate vaccine, accurate N. meningitidis serogroup determination is key. To this end, we developed and evaluated two duplex rapid diagnostic tests (RDTs) for detecting N. meningitidis polysaccharide (PS) antigens of several important serogroups. METHODS AND FINDINGS: Mouse monoclonal IgG antibodies against N. meningitidis PS A, W135/Y, Y, and C were used to develop two immunochromatography duplex RDTs, RDT1 (to detect serogroups A and W135/Y) and RDT2 (to detect serogroups C and Y). Standards for Reporting of Diagnostic Accuracy criteria were used to determine diagnostic accuracy of RDTs on reference strains and cerebrospinal fluid (CSF) samples using culture and PCR, respectively, as reference tests. The cutoffs were 10(5) cfu/ml for reference strains and 1 ng/ml for PS. Sensitivities and specificities were 100% for reference strains, and 93.8%-100% for CSF serogroups A, W135, and Y in CSF. For CSF serogroup A, the positive and negative likelihood ratios (+/- 95% confidence intervals [CIs]) were 31.867 (16.1-63.1) and 0.065 (0.04-0.104), respectively, and the diagnostic odds ratio (+/- 95% CI) was 492.9 (207.2-1,172.5). For CSF serogroups W135 and Y, the positive likelihood ratio was 159.6 (51.7-493.3) Both RDTs were equally reliable at 25 degrees C and 45 degrees C. CONCLUSIONS: These RDTs are important new bedside diagnostic tools for surveillance of meningococcus serogroups A and W135, the two serogroups that are responsible for major epidemics in Africa.

Simple alternative to sialic acid determination in meningococcal polysaccharides W or Y.

Physicochemical methods are the primary tests used to ensure that batches of meningococcal polysaccharide (PS) antigens are manufactured consistently to those shown to be safe and effective in clinical trials. Although modern physicochemical methods of analysis providing structural information about the antigens have been developed and used, simpler assays, which can be readily validated, are still in use for polysaccharide batch release. The simple and cheap method for Neisseria meningitidis serogroup W or Y polysaccharide (MenW or MenY PS) content quantification has been developed. This colorimetric method is based on the galactose or glucose quantification in MenW or MenY PS hydrolysate, respectively. Intra- and inter-assay precision and accuracy of the novel method have been demonstrated, in comparison to the same properties of the current regulatory approved method for the same purpose - sialic acid quantification. We provided the calculation of the possible future regulatory requirement for the galactose or glucose content in MenW or MenY PS, respectively, and revealed in detail the stoichiometric calculation behind it.

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013.

Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogroup A has been prevalent in the African "meningitis belt" whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journal (1) , an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions.

Meningococcal meningitis with meningococcemia: a rare sporadic case in an elderly patient with no history of contact with infected individuals.

An 89-year-old Japanese woman with no history of contact with infected individuals developed meningococcal meningitis with meningococcemia. Compared with other countries, invasive meningococcal disease is relatively rare in Japan, with an annual incidence of a total of 10-20 cases for more than 2 decades; this represents approximately 1% of the corresponding incidence in the United States and United Kingdom. The most prevalent serotypes of the causative agent Neisseria meningitidis in Japan are serotypes B and Y. The patient in this study was also infected with a strain of serotype Y. The meningococcal vaccine has not yet been approved for use in Japan. The only possible transmission route in this patient was a visit by the patient's grandchild a few days prior to the onset of symptoms. Due to its low incidence, clinicians do not have sufficient experience for managing this potentially fatal illness. This case highlights the need for considering a complete differential diagnosis of invasive meningococcal disease.

Meningococcal serogroup Y emergence in Europe: high importance in some European regions in 2012.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. (1)(,) (2) Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.