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.

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.

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.

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.

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.

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.

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.

Meningococcal serogroup Y lpxL1 variants from South Africa are associated with clonal complex 23 among young adults.

OBJECTIVES: To determine the genotypes of serogroup Y meningococcus (MenY), and to determine the prevalence of and identify factors associated with MenY lpxL1 variants. METHODS: Isolates, collected from 2003 to 2007 through national surveillance for invasive meningococcal disease, were characterized by multilocus sequence typing and screened for interleukin-6 induction. LpxL1 genes were sequenced from low IL-6 inducers. RESULTS: MenY represented 13% (n = 219/1702) of meningococcal disease. Clonal complex (cc) 175, ST-23/Cluster A3 (cc23), cc11 and cc167 accounted for 82% (176/214), 11% (24/214), 3% (6/214) and 3% (7/214) respectively. Low cytokine induction was evident in 15% (32/218). Cc23 isolates (24/24) had an lpxL1 mutation, while among the remaining isolates the proportion of lpxL1 variants was 4% (8/189, p < 0.001), and these were all cc175. Compared to wild type isolates, lpxL1 variants were associated with patients aged 5-14 years [unadjusted OR (95% CI): 4.3 (1.5-12)] or 15-24 years [unadjusted OR (95% CI): 9.1 (2.8-29)] compared to children <5 years; and were more likely have been isolated from CSF than blood [unadjusted OR (95% CI): 3.5 (1-11.9)]. On multivariable analysis, age remained significant [adjusted OR (95% CI), 5-14 years: 4.2 (1.5-12); 15-24 years: 8.9 (2.7-29)]. CONCLUSION: LpxL1 variants were associated with cc23 among young adults.

Meningococcal septic shock after IUD insertion, a case presentation.

Neisseria meningitidis is a normal commensal of human mucous membranes that is no longer considered to be restricted to the nasopharynx. Due to the practice of oral sex, the mucous membranes of the cervix, urethra or anus have become a potential infection site for this bacterium. Inserting an intrauterine device (IUD), can alter the protective barrier of the endocervical mucosa, allowing for bacterial infection and systemic spread. We present a case report of a 40-year-old woman who presented with abdominal pain, spotting and fever after inserting an IUD and developed a fulminant septic shock. Blood cultures and cultures from ascites showed the presence of Neisseria meningitidis group Y. From our knowledge, there are a few cases presented in the literature of toxic shock syndrome after IUD insertion, caused by Staphylococcus aureus or Streptococcus group A, but this is the first case of meningococcal sepsis after IUD insertion described. So, even though IUDs rarely cause significant infection, physicians should consider this device as a possible source in reproductive-age women with the clinical features of sepsis.

Meningococcal serogroup Y emergence in Europe: update 2011.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W-135, 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 from various European countries previously published in this journal. ( 1) Here, data is reported indicating that the emergence of serogroup Y continued in 2011 in various regions of Europe. The average age of persons affected by N. meningitidis serogroup Y seems to have decreased in some countries in comparison to the previous decade.

[Neisseria meningitidis: characterisation and epidemiology]. / Bactériologie de Neisseria meningitidis.

Neisseria meningitidis are Gram-negative cocci, whose reservoir is exclusively human. This bacterium has several virulence factors including capsule with antiphagocytic properties, lipopolysaccharide, iron uptake system, pili and an IgA1 protease. The strains can be typed by immunological or genotypic methods. Phenotypic determination defines the serogroup, serotype, subtype and immunotype. Molecular typing, a very discriminating method, allows the determination of clonal complexes. These two epidemiological approaches allow the characterization of N. meningitidis strains. Conversely to the other strains, invasive strains belong to a very limited number of clonal complexes (CC). The evolution of the genome of N. meningitidis is the consequence of horizontal transfer of DNA occurring by transformation or recombination and leading to capsular exchanges. The distribution of the different serogroups varies according to the different countries. In France, in 2010, the serogroups B, C, W135 and Y accounted respectively for 72%, 17%, 5% and 2% of cases of invasive infections. The recent emergence of serogroup X in Niger highlights the need for continuing epidemiological surveillance.

Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States.

In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average π(N)  =  0.0033 and average π(S)  =  0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease.

Meningococcal polysaccharide vaccine failure in a patient with C7 deficiency and a decreased anti-capsular antibody response.

A 20-y-old male presented with symptoms of meningococcal sepsis and died despite appropriate medical interventions. Blood cultures grew N. meningitidis serogroup Y. The patient had received the meningococcal quadrivalent (A,C,W-135,Y) polysaccharide vaccine 15 mo previously. Because the patient had a history of meningococcal meningitis at age 10, archived serum was obtained for further analysis. Complement component C7 was found to be deficient, and antibody levels to meningococcal polysaccharides were undetectable for two serogroups and low for the infecting serogroup 10 mo post-vaccination. This case highlights the fact that some individuals with terminal complement component deficiencies mount an impaired or short-lived response to vaccination with meningococcal capsular polysaccharides, and underscores the appropriateness of a more aggressive vaccination strategy in this patient population.

Increase of meningococcal serogroup Y cases in Europe: a reason for concern?

Neisseria meningitidis is differentiated into 12 distinct serogroups of which A, B, C, W-135, X and Y are medically most important and represent a major health problem in one or more parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. A sudden increase or decrease of IMD or meningococcal carriage may occur anywhere at any time. Recent epidemiological surveillance indicates an increase of serogroup Y IMD in some parts of Europe and data from various European countries are presented.