Biofilm Formation by Nontypeable Haemophilus Influenzae and Resistance to Complement-Mediated Clearance.

Biofilm formation has been suggested to be associated with phenotype changes compared with the planktonic form. We screened 1092 Haemophilus influenzae isolates for their genetic relationships and then selected 29 isolates from different genotypes and phenotypes and tested their ability to form biofilm. Our data showed a higher capacity of nontypable isolates, particularly isolates from respiratory and genital infections to form biofilm, compared with typable isolates. This ability to form biofilm was also correlated with reduced deposition of the complement component C3b on biofilm-involved bacteria. These data suggest that the biofilm formation contributes to the virulence of nontypable H. influenzae.

Detection of CTX-M-15 ESBL in XDR Haemophilus parainfluenzae from a urethral swab.

OBJECTIVES: Haemophilus parainfluenzae is an opportunistic pathogen causing respiratory tract infection and sexually transmitted diseases. The emergence of multidrug resistance in this species is particularly worrisome, especially since the recent description of CTX-M-15 ESBL-producing isolates in Spain. The aim of this study was to characterize a CTX-M-15-producing H. parainfluenzae clinical isolate, HP01, obtained from a urethral swab. METHODS: MICs were determined with gradient strips for this isolate. Hydrolysis assays were performed with the ß LACTA test. Genomic DNA from HP01 was subjected to Illumina and Oxford Nanopore sequencing to investigate the genetic environment of blaCTX-M-15. Phylogenetic analysis was performed with available H. parainfluenzae genomes from the NCBI database, including CTX-M-15 producers. RESULTS: HP01, an XDR isolate, was resistant to penicillin, third-generation cephalosporins, fluoroquinolones, macrolides, cyclines and co-trimoxazole and susceptible only to carbapenems and rifampicin. HP01 carried blaTEM-1, blaCTX-M-15, tet(M), catS and mef(E)/mel and harboured amino acid substitutions in PBP3, PBP5, GyrA, ParC and FolA implicated in resistance. Genomic analysis revealed that blaCTX-M-15 was carried by a Tn3-like transposon inserted into a novel integrative and conjugative element (ICE), ICEHpaSLS, present on the chromosome and belonging to the ICEHin1056 family described in Haemophilus influenzae. The tet(M)-MEGA element was also detected on the chromosome. No plasmid was found. The phylogenetic analysis showed that four H. parainfluenzae producing CTX-M-15 clustered in the same clade. CONCLUSIONS: Here we report the description of an XDR H. parainfluenzae producing blaCTX-M-15 isolated from a urethral swab. The blaCTX-M-15 gene was inserted into an ICE structure similar to those recently described in CTX-M-15 producers in Spain. The emergence of XDR H. parainfluenzae producing blaCTX-M-15 is a matter of great concern. Careful surveillance is required to prevent its spread.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

Recent increase in atypical presentations of invasive meningococcal disease in France.

BACKGROUND: Invasive meningococcal disease (IMD) cases declined upon the implementation of non-pharmaceutical interventions (NPI) (social distancing and mask wearing) to control the COVID-19 pandemic but rebounded in 2022 in numbers with genotypical changes of the strains. We explored here associated modifications in the clinical presentations of IMD. METHODS: We conducted a retrospective descriptive study using the Database of the French National Reference Centre for meningococci and Haemophilus influnezae for IMD cases between 2015 and 2022. We scored serogroups, sex, age groups, clinical presentations and clonal complexes of the corresponding patients and isolates. FINDINGS: Non-meningeal forms of IMD increased significantly upon easing of NPI, such as bacteremic meningococcal pneumonia and bacteremic abdominal forms. They represented 6% and 8% of all IMD forms and were significantly linked to serogroups Y and W respectively, to older adults for bacteremic pneumonia and to young adults for bacteremic abdominal presentations. These forms were significantly associated with more early mortality and clonal complexes 23, 11 and 9316. INTERPRETATION: The increase in atypical IMD forms may lead to higher burden of IMD due to delayed diagnosis and management. Updating prevention may be needed through by adapting the current vaccination strategies to epidemiological changes.

Haemophilus influenzae type b (Hib) seroprevalence in France: impact of vaccination schedules.

BACKGROUND: Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in France in 1992 as a 3 + 1 scheme at 2, 3, and 4 months (primary vaccination) with a booster at the age of 16-18 months. The vaccination was simplified in 2013 to a 2 + 1 scheme at 2 and 4 months (primary immunization) and a booster at the age of 11 months. The coverage was 95.4% in France at 24 months in 2017. During the period 2017-2019 the number of Hib invasive infections increased with several cases of vaccine failure. METHODS: The numbers and proportions of Hib invasive isolates during the period 2017-2019 were compared and vaccine failure cases were explored. A seroprevalence study was performed by measuring anti-polyribosyl-ribitol phosphate (PRP) IgG concentrations by ELISA among children < 5 years of age at the time of sampling covering the periods of the 3 + 1 or 2 + 1 schemes of Hib vaccination. A collection of residual 232 sera was tested (group 3 + 1 n = 130) and (group 2 + 1, n = 102) was used. RESULTS: Anti-PRP IgG concentrations were significantly higher in toddlers of 2 years (median 2.9 µg/ml) in the 3 + 1 group while these concentrations showed a median of 0.58 µg/ml among children in 2 + 1 group. The proportion of children of 2 years of age who achieved 1 µg/ml threshold (56%) was higher in the 3 + 1 group than that observed in the 2 + 1 group (25%). All the detected cases of vaccine failure received the 2 + 1 scheme and anti-PRP IgG levels were less than 1 µg/ml at the admission. However, these levels increased significantly 1 month after the admission suggesting a secondary immune response to the Hib infection. CONCLUSIONS: The simplification of the vaccination to a 2 + 1 scheme seems to reduce the level of anti PRP IgG. Hib antibodies wane rapidly after the 11 months booster and may not be enough to ensure long term protection. Surveillance of cases and monitoring of titres need to be continued to inform future vaccination policy.

Transmissibility and pathogenicity of the emerging meningococcal serogroup W sequence type-11 complex South American strain: a mathematical modeling study.

BACKGROUND: The recent emergence of strains belonging to the meningococcal serogroup W (MenW) sequence type-11 clonal complex and descending from the South American sub-lineage (MenW:cc11/SA) has caused significant shifts in the epidemiology of meningococcal disease worldwide. Although MenW:cc11/SA is deemed highly transmissible and invasive, its epidemiological characteristics have not yet been quantified. METHODS: We designed a mathematical model of MenW transmission, carriage, and infection to analyze the recent epidemiology of invasive disease caused by MenW:cc11/SA strains and by other MenW strains in England and in France. We confronted that model with age-stratified incidence data to estimate the transmissibility and the invasiveness of MenW:cc11/SA in England, using the data in France as a validation cohort. RESULTS: During the epidemiological years 2010/2011-2014/2015 in England, the transmissibility of MenW:cc11/SA relative to that of other MenW strains was estimated at 1.20 (95% confidence interval, 1.15 to 1.26). The relative invasiveness of MenW:cc11/SA was also found to exceed unity and to increase with age, with estimates ranging from 4.0 (1.6 to 9.7) in children aged 0-4 years to 20 (6 to 34) in adults aged ≥ 25 years. In France, the model calibrated in England correctly reproduced the early increase of MenW:cc11/SA disease during 2012/2013-2016/2017. Most recent surveillance data, however, indicated a decline in MenW:cc11/SA disease. In both countries, our results suggested that the transmission of MenW:cc11/SA carriage possibly started several months before the first reported case of MenW:cc11/SA disease. DISCUSSION: Our results confirm earlier suggestions about the transmission and the pathogenic potential of MenW:cc11/SA. The main limitation of our study was the lack of age-specific MenW carriage data to confront our model predictions with. Furthermore, the lesser model fit to the most recent data in France suggests that the predictive accuracy of our model might be limited to 5-6 years. CONCLUSIONS: Our study provides the first estimates of the transmissibility and of the invasiveness of MenW:cc11/SA. Such estimates may be useful to anticipate changes in the epidemiology of MenW and to adapt vaccination strategies. Our results also point to silent, prolonged transmission of MenW:cc11/SA carriage, with potentially important implications for epidemic preparedness.

Validation of a New Rapid Detection Test for Detection of Neisseria meningitidis A/C/W/X/Y Antigens in Cerebrospinal Fluid.

Meningococcal meningitis remains a life-threatening disease worldwide, with high prevalence in the sub-Saharan meningitis belt. A rapid diagnosis is crucial for implementing adapted antimicrobial treatment. We describe the performances of a new immunochromatographic test (MeningoSpeed, BioSpeedia, France) for detecting and grouping Neisseria meningitidis Cerebrospinal fluids (CSFs) were collected from 5 African countries and France. For the rapid diagnostic test (RDT), the CSF sample was deposited on each of the 3 cassettes for a total volume of 90 µl. The results of the RDT were compared to those of a reference multiplex PCR assay detecting the major serogroups of N. meningitidis on 560 CSF specimens. Five specimens were found uninterpretable by RDT (0.9%). The results of interpretable specimens were as follows: 305 positive and 212 negative samples by both techniques, 14 positive by PCR only, and 24 positive by RDT only (sensitivity, specificity, and positive and negative predictive values of 92.7%, 93.8%, 95.6%, and 89.8%, respectively, with an accuracy of 93.2% and a kappa test of 0.89; P < 0.05). From 319 samples positive by PCR for serogroups A, C, W, X, or Y, the grouping results were concordant for 299 specimens (sensitivity of 93.0%, 74.4%, 98.1%, 100%, and 83.3% for serogroups A, C, W, X, and Y, respectively). The MeningoSpeed RDT exhibited excellent performances for the rapid detection of N. meningitidis antigens. It can be stored at room temperature, requires a minimal amount of CSF, is performed in 15 minutes or less, and is easy to use at bedside.

Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice.

BACKGROUND: Neisseria meningitidis serogroups W and Y are the most common serogroups causing invasive meningococcal disease in Sweden. The majority of cases are caused by the serogroup W UK 2013 strain of clonal complex (cc) 11, and subtype 1 of the serogroup Y, YI strain of cc23. In this study, virulence factors of several lineages within cc11 and cc23 were investigated in transgenic BALB/c mice expressing human transferrin. Transgenic mice were infected intraperitoneally with serogroup W and Y isolates. Levels of bacteria and the proinflammatory cytokine CXCL1 were determined in blood collected 3 h and 24 h post-infection. Apoptosis was investigated in immune cells from peritoneal washes of infected mice. Adhesion and induction of apoptosis in human epithelial cells were also scored. RESULTS: The levels of bacteraemia, CXCL1, and apoptosis were higher in serogroup W infected mice than in serogroup Y infected mice. Serogroup W isolates also induced higher levels of apoptosis and adhesion in human epithelial cells. No significant differences were observed between different lineages within cc11 and cc23. CONCLUSIONS: N. meningitidis Serogroup W displayed a higher virulence in vivo in transgenic mice, compared to serogroup Y. This was reflected by higher bacteremia, proinflammatory activity, and ability to induce apoptosis in mouse immune cells and human epithelial cells.

First report of meningococcal ciprofloxacin resistance in Greece due to invasive isolates of the sequence type ST-3129.

A local outbreak caused by Neisseria meningitidis occurred in the migration camp in the Greek island of Lesbos during January-February 2020 (4 of 5 cases). In total, 5 samples positive for N. meningitidis were further investigated for sero-/genogroup, PorA, and WGS analysis. MenB was found among 3 cases, while in two cases, MenY was identified. WGS analysis and antibiotic susceptibility testing on the 2 culture positive MenB samples showed the new ST-3129, ciprofloxacin-resistant clone was circulating among the immigrants in the aforementioned camp. This is the first report of ciprofloxacin resistance in Greece.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

BACKGROUND: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation. METHODS: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine. RESULTS: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported. CONCLUSIONS: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

A step-by-step in crystallo guide to bond cleavage and 1,6-anhydro-sugar product synthesis by a peptidoglycan-degrading lytic transglycosylase.

Lytic transglycosylases (LTs) are a class of enzymes important for the recycling and metabolism of peptidoglycan (PG). LTs cleave the ß-1,4-glycosidic bond between N-acetylmuramic acid (MurNAc) and GlcNAc in the PG glycan strand, resulting in the concomitant formation of 1,6-anhydro-N-acetylmuramic acid and GlcNAc. No LTs reported to date have utilized chitins as substrates, despite the fact that chitins are GlcNAc polymers linked via ß-1,4-glycosidic bonds, which are the known site of chemical activity for LTs. Here, we demonstrate enzymatically that LtgA, a non-canonical, substrate-permissive LT from Neisseria meningitidis utilizes chitopentaose ((GlcNAc)5) as a substrate to produce three newly identified sugars: 1,6-anhydro-chitobiose, 1,6-anhydro-chitotriose, and 1,6-anhydro-chitotetraose. Although LTs have been widely studied, their complex reactions have not previously been visualized in the crystalline state because macromolecular PG is insoluble. Here, we visualized the cleavage of the glycosidic bond and the liberation of GlcNAc-derived residues by LtgA, followed by the synthesis of atypical 1,6-anhydro-GlcNAc derivatives. In addition to the newly identified anhydro-chitin products, we identified trapped intermediates, unpredicted substrate rearrangements, sugar distortions, and a conserved crystallographic water molecule bound to the catalytic glutamate of a high-resolution native LT. This study enabled us to propose a revised alternative mechanism for LtgA that could also be applicable to other LTs. Our work contributes to the understanding of the mechanisms of LTs in bacterial cell wall biology.

Unusual Initial Abdominal Presentations of Invasive Meningococcal Disease.

Background: Invasive meningococcal disease (IMD) is recognized as septicemia and/or meningitis. However, early symptoms may vary and are frequently nonspecific. Early abdominal presentations have been increasingly described. We aimed to explore a large cohort of patients with initial abdominal presentations for association with particular meningococcal strains. Methods: Confirmed IMD cases in France between 1991 and 2016 were screened for the presence within the 24 hours before diagnosis of at least 1 of the following criteria (1) abdominal pain, (2) gastroenteritis with diarrhea and vomiting, or (3) diarrhea only. Whole-genome sequencing was performed on all cultured isolates. Results: We identified 105 cases (median age, 19 years) of early abdominal presentations with a sharp increase since 2014. Early abdominal pain alone was the most frequent symptom (n = 67 [64%]), followed by gastroenteritis (n = 26 [25%]) and diarrhea alone (n = 12 [11%]). Twenty patients (20%) had abdominal surgery. A higher case fatality rate (24%) was observed in these cases compared to 10.4% in all IMD in France (P = .007) with high levels of inflammation markers in the blood. Isolates of group W were significantly more predominant in these cases compared to all IMD. Most of these isolates belonged to clonal complex 11 of the sublineages of the South American-UK strain. Conclusions: Abdominal presentations are frequently provoked by hyperinvasive isolates of meningococci. Delay in the management of these cases and the virulence of the isolates may explain the high fatality rate. Rapid recognition is a key element to improve their management.

Emergence of Neisseria meningitidis Serogroup W, Central African Republic, 2015-2016.

We analyzed data from the 2015 and 2016 meningitis epidemic seasons in Central African Republic as part of the national disease surveillance. Of 80 tested specimens, 66 belonged to meningococcal serogroup W. Further analysis found that 97.7% of 44 isolates belonged to the hyperinvasive clonal complex sequence type 11.

Acquisition of Beta-Lactamase by Neisseria meningitidis through Possible Horizontal Gene Transfer.

We report the detection in France of a beta-lactamase-producing invasive meningococcal isolate. Whole-genome sequencing of the isolate revealed a ROB-1-type beta-lactamase gene that is frequently encountered in Haemophilus influenzae, suggesting horizontal transfer between isolates of these bacterial species. Beta-lactamases are exceptional in meningococci, with no reports for more than 2 decades. This report is worrying, as the expansion of such isolates may jeopardize the effective treatment against invasive meningococcal disease.

Molecular Characterization of Invasive Isolates of Neisseria meningitidis in Casablanca, Morocco.

Meningococcal epidemiology may change unpredictably, and typing of Neisseria meningitidis isolates is crucial for the surveillance of invasive meningococcal disease (IMD). Few data are available regarding the meningococcal epidemiology in countries of North Africa. We aimed to explore invasive meningococcal isolates from the Casablanca region in Morocco. We used whole-genome sequencing (WGS) to characterize 105 isolates from this region during the period of 2011 to 2016. Our data showed that the majority (n = 100) of the isolates belonged to serogroup B. Genotyping indicated that most of the isolates (n = 62) belonged to sequence type 33 of clonal complex 32. The isolates also showed the same PorA and FetA markers and clustered together on the basis of WGS phylogenetic analysis; they seemed to correspond to an expansion of local isolates in the Casablanca region, as reported for similar isolates in several other countries. These data suggest that serogroup B isolates may predominate in Morocco, which may have an important impact in the design of vaccination strategies.

Primary bacterial ventriculitis in adults, an emergent diagnosis challenge: report of a meningoccal case and review of the literature.

BACKGROUND: Defined by an infection of the ventricular system of the brain, ventriculitis is usually known as a health-care associated infection. In contrast, primary pyogenic ventriculitis complicating community-acquired meningitis is uncommon, and mainly described in infants. Only seven cases that have occured in adults have been found in the international literature. CASE PRESENTATION: We report here a new case due to Neisseria meningitidis occurring in an 85 year-old-man. The comparison with previous reports allows to drawn several conclusions: (i) cases occurred in relatively old adults (median age: 65 years); (ii) Streptococcus pneumoniae, N. meningitiditis and Staphylococcus aureus are the leading responsible pathogens; (iii) atypical clinical presentation seems the rule in which meningism often lacks; (iv) in absence of clinical or biological specific parameters, modern brain imaging such as magnetic resonance imaging with gadolinium enhancement is of utmost importance for the diagnosis, leading to anticipate an increase of the diagnosis in the near future, thanks to easier access to such exploration; (v) death or serious sequelae commonly occurred; (vi) prolonged antibiotic courses (6 weeks to 3 months) have been used, without strong rational. In the given case, the patient presented with a lack of meningeal irritation signs. The diagnosis was made by MRI considering a lasting confused state. A four-week antibiotic regimen was successful, combining two weeks of intravenous cefotaxime followed by two weeks of oral levofloxacin much easier to administrate and allowing early rehabilitation. CONCLUSION: Primary bacterial ventriculitis is a real diagnosis challenge. Larger indications of MRI for bacterial meningitis, particularly in cases with an atypical presentation or poor evolution would certainly increase the number of diagnosis.

Common Cell Shape Evolution of Two Nasopharyngeal Pathogens.

Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) and a cell shape change from rod to cocci had been selected for along the past evolution of N. meningitidis. Using genomic comparison across species, we correlated the emergence of the new cell shape (cocci) with the deletion, from the genome of N. meningitidis ancestor, of only one gene: yacF. Moreover, the reconstruction of this genetic deletion in a bacterium harboring the ancestral version of the locus together with the analysis of the PG structure, suggest that this gene is coordinating the transition from cell elongation to cell division. Accompanying the loss of yacF, the elongation machinery was also lost by several of the descendants leading to the change in the PG structure observed in N. meningitidis. Finally, the same evolution was observed for the ancestor of M. catarrhalis. This suggests a strong selection of these genetic events during the colonization of the nasopharynx. This selection may have been forced by the requirement of evolving permissive interaction with the immune system, the need to reduce the cellular surface exposed to immune attacks without reducing the intracellular storage capacity, or the necessity to better compete for adhesion to target cells.

Community outbreak of serogroup B invasive meningococcal disease in Beaujolais, France, February to June 2016: from alert to targeted vaccination.

In February and March 2016, four cases of serogroup B invasive meningococcal disease (IMD) occurred over 3 weeks in a small area north of Lyon in the Auvergne-Rhône-Alpes region, France. There were no deaths but two cases had sequelae. This community outbreak was caused by a rare meningococcal strain of the clonal complex ST-32, covered by the 4CMenB/Bexsero vaccine. The incidence rate for serogroup B IMD in this area was 22.5 per 100,000 inhabitants, which is above the epidemic threshold (10/100,000). The number of cases observed was significantly higher than expected in the age group of 0-24 year-olds (standardised incidence ratio: 96). These results suggested the potential emergence of this invasive strain in this sub-population. In accordance with French recommendations, it was decided to vaccinate the population aged between 2 months and 24 years, living, working or studying in the epidemic area. The vaccination campaign took place from April to September 2016. Vaccination coverage was estimated at 47% for one dose and 40% for two doses. The lowest coverage estimations were observed for the age groups younger than 3 and 15-19 years. Enhanced epidemiological and microbiological surveillance reported a fifth case in June 2016, outside the epidemic area.

Establishment of the European meningococcal strain collection genome library (EMSC-GL) for the 2011 to 2012 epidemiological year.

Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation.