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.

Epidemiological and bacterial profile of childhood meningitis in Tunisia.

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns.The aim of our study was to evaluate the epidemiological and bacteriological profile of paediatric bacterial meningitis (BM) in Tunisian children, during the period 2003-2019, following the implementation of Haemophilus influenzae type b (Hib) vaccine (April 2011) and before 10-valent pneumoccocal conjugate vaccine (PCV10) introduction to the childhood immunization program.All bacteriologically confirmed cases of BM admitted to children's hospital of Tunis were recorded (January 2003 to April 2019). Serogroups of Neisseria meningitidis (Nm) and serotypes of Streptococcus pneumoniae (Sp) and H. influenzae (Hi) and antibiotic resistance were determined using conventional and molecular methods.Among 388 cases, the most frequent species were Sp (51.3%), followed by Nm (27.5%) and Hi (16.8%). We observed a significant decrease in Hi BM rate during the conjugated Hib vaccine use period (P < 0.0001). The main pneumococcal serotypes were 14, 19F, 6B, 23F and 19A and the serotype coverage of PCV10, PCV13, PCV15 and PCV20 was 71.3 and 78.8%, 79.4 and 81.9% respectively. The most frequent Nm serogroup was B (83.1%). Most Hi strains were of serotype b (86.9%). High levels of resistance were found: Sp and Nm to penicillin (respectively 60.1 and 80%) and Hi to ampicillin (42.6%). All meningococcal and Hi isolates were susceptible to third-generation cephalosporins and 7.2% of pneumococcal strains had decreased susceptibility to these antibiotics.The Hib conjugate vaccine decreased the rate of BM. Sp dominated the aetiology of BM in children in Tunisia. Conjugate vaccines introducing decreases not only BM cases but also antimicrobial resistance.

Genomic surveillance of Neisseria meningitidis serogroup W in Portugal from 2003 to 2019.

In recent years, a change in the epidemiology of meningococcal disease caused by Neisseria meningitidis serogroup W (MenW) has been observed worldwide, with the emergence of new sublineages associated with a higher rate of fatal cases. The present study intends to describe the epidemiology of invasive meningococcal disease (IMD) due to MenW in Portugal between 2003 and 2019, and to genetically characterize population structure. Despite MenW has a low incidence in Portugal, having almost disappeared from 2008 to 2015, since 2016, the number of MenW cases has been steadily increasing at a rate of ~ twofold per year, with more than 80% of the characterized isolates belonging to clonal complex 11 (cc11). Core-genome phylogeny of 25 Portuguese (PT) MenW isolates showed a strain clustering mainly either with the Original UK or the UK 2013 sublineages. Our study also reported for the first time the presence of distinct prophages with a notable overrepresentation of an ~ 32-35-kb PS_1-like prophage found in MenW cc11 genomes. The presence of the PS_1-like prophage in almost all 4723 cc11 genomes selected from Neisseria PubMLST database regardless of the capsular group they belong to suggests an ancestral acquisition of this mobile element prior to capsular switching events. Overall, by mimicking the scenario observed worldwide, this study reinforces the importance of a close monitoring of MenW disease, especially from cc11, in order to promptly adapt the vaccination plan for IMD control in Portugal. Moreover, future studies are needed to understand the putative contribution of prophages to fitness and virulence of PT MenW strains.

Emergence of a novel urogenital-tropic Neisseria meningitidis.

PURPOSE OF REVIEW: Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US_NmUC). This review describes research developments that characterize this urogenital-tropic Nm. RECENT FINDINGS: The US_NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US_NmUC urethritis episodes can occur. The US_NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance. SUMMARY: The US_NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined.

Carbohydrate based meningococcal vaccines: past and present overview.

Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive strains are surrounded by a polysaccharide capsule, based on which, 12 N. meningitidis serogroups are differentiated. Six of them, A, B, C, W, X, and Y, cause the vast majority of infections in humans. Mono- and multi-valent carbohydrate-based vaccines against meningococcal infections have been licensed or are currently in clinical development. In this mini-review, an overview of the past and present approaches for producing meningococcal glycoconjugate vaccines is provided.

Development and Immunogenicity of a Brazilian Glycoconjugate vaccine against Meningococcal W in a Pilot Scale.

Recent changes in the epidemiology of meningococcal have been reported and meningococcal group W (MenW) has become the third most prevalent group isolated in Brazil in the last 10 years. In this study we have developed a conjugate vaccine for MenW using a modified reductive amination conjugation method through a covalent linkage between periodate-oxidized MenW non-O-acetylated polysaccharide and hydrazide-activated monomeric tetanus toxoid. Process control of bulks was done by physicochemical analysis including polysaccharide and protein quantification, high performance liquid chromatography - size exclusion chromatography, capillary electrophoresis, and hydrogen nuclear magnetic resonance. Conjugate bulks were best produced with concentration of polysaccharide twice as high as protein, at room temperature, and pH approximately 6.0. A scaled-up bulk (100 mg scale) was formulated and inoculated intramuscularly in mice in a dose-response study (0.1, 0.5, 1.0 and 10.0 µg of polysaccharide/dose). The immunogenicity of conjugate bulks was determined by serum bactericidal assay and ELISA assays of serum from immunized mice. ELISA and SBA titers revealed high titers of IgG and demonstrated the functionality of the antibodies produced in all doses studied 15 days after the third dose. However, significant differences were observed among them by ELISA. In conclusion, this study established the best conditions to produce MenW conjugate bulks and showed the efficacy of the obtained conjugate bulk in induce a good immune response in mice. Further experiments will need to be done to scale up the conjugation reaction and then allow the use of this conjugate in clinical trials.

Antibiotic susceptibility and molecular analysis of invasive Neisseria meningitidis recovered in the Republic of Ireland, 1996 to 2016.

This study examined the antimicrobial susceptibility of invasive meningococcal disease (IMD)-associated Neisseria meningitidis recovered in the Republic of Ireland between 1996 and 2016. In total, 1359 isolates representing over one-third of all laboratory-confirmed cases of IMD diagnosed each epidemiological year (EY; July 1-June 30) were analysed. All isolates were susceptible to ciprofloxacin, rifampicin and cefotaxime and 74% and 87% were susceptible to sulphonamide and penicillin, respectively. The proportion of isolates exhibiting reduced susceptibility to penicillin increased significantly during the study with no evidence of major clonal expansion or horizontal spread of a specific penA allele. Greater diversity observed among recently recovered meningococci and specifically among isolates exhibiting reduced penicillin susceptibility contributed to the overall increase in penA allele diversity throughout. The emergence and dissemination of strains with phenotypic and genotypic reduced susceptibility to penicillin increase the need for continued surveillance of antimicrobial susceptibility of meningococci in the Republic of Ireland especially in view of the recommendation of penicillin G as empiric treatment of choice for pre-hospital management.

Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa.

In the African meningitis belt, a region of sub-Saharan Africa comprising 22 countries from Senegal in the west to Ethiopia in the east, large epidemics of serogroup A meningococcal meningitis have occurred periodically. After gradual introduction from 2010 of mass vaccination with a monovalent meningococcal A conjugate vaccine, serogroup A epidemics have been eliminated. Starting in 2013, the northwestern part of Nigeria has been affected by yearly outbreaks of meningitis caused by a novel strain of serogroup C Neisseria meningitidis (NmC). In 2015, the strain spread to the neighboring country Niger, where it caused a severe epidemic. Following a relative calm in 2016, the largest ever recorded epidemic of NmC broke out in Nigeria in 2017. Here, we describe the recent evolution of this new outbreak strain and show how the acquisition of capsule genes and virulence factors by a strain previously circulating asymptomatically in the African population led to the emergence of a virulent pathogen. This study illustrates the power of long-read whole-genome sequencing, combined with Illumina sequencing, for high-resolution epidemiological investigations.

Evolutionary analysis of gyrA gene from Neisseria meningitidis bacterial strains of clonal complex 4821 collected in China between 1978 and 2016.

BACKGROUND: Neisseria meningitidis (N.meningitidis) bacteria belonging to clonal complex 4821 (CC4821) have been mainly reported in China and have been characterized by a high resistance rate to ciprofloxacin (CIP). The aim of this study was to assess the evolution of the DNA gyrase A (gyrA) gene from N.meningitidis CC4821 strains collected in China between 1978 and 2016. The complete sequence of gyrA gene from 77 strains are reported in this study and analyzed in the context of publicly available sequences from N. meningitidis of other CCs as well as other Neisseria species. RESULTS: The phylogenetic analysis of CC4821 gyrA gene reveals at least 5 distinct genetic clusters. These clusters are not CC4821-specific showing that gyrA evolution is independent of CC4821 evolution. Some clusters contain sequences from other Neisseria species. Recombination within N.meningitidis strains and between Neisseria species was identified in SimPlot analysis. Finally, amino acid substitutions within GyrA protein were analyzed. Only one position, 91 (83 in E.coli gyrA gene), was linked to CIP resistance. Thirty-one additional putative resistance markers were identified, as amino acid substitutions were only found in resistant strains. CONCLUSIONS: The evolution of gyrA gene of CC4821 N.meningitidis strains is not dependent on CC4821 evolution or on CIP resistance phenotype. Only amino acid 91 is linked to CIP resistance phenotype. Finally, recombination inter- and intra-species is likely to result in the acquisition of various resistance markers, 31 of them being putatively mapped in the present study. Analyzing the evolution of gyrA gene within CC4821 strains is critical to monitor the CIP resistance phenotype and the acquisition of new resistance markers. Such studies are necessary for the control of the meningococcal disease and the development of new drugs targeting DNA gyrase.

Repeat Episodes of Symptomatic Urethritis Due to a Uropathogenic Meningococcal Clade.

In 2015, we identified a non-groupable clade of Neisseria meningitidis that causes urethritis in men (the US_NmUC). Because repeat infection is common with Neisseria gonorrhoeae, we examined whether reinfection also occurs with the US_NmUC. We provide evidence that men are susceptible to repeat episodes of urethritis from the US_NmUC.

Atypical presentation of invasive meningococcal disease caused by serogroup W meningococci.

Neisseria meningitidis, a gram-negative diplococcus, is typically an asymptomatic coloniser of the oropharynx and nasopharynx. Passage of N. meningitidis into the bloodstream can cause invasive meningococcal disease (IMD), a potentially life-threatening illness with rapid onset that generally presents as meningitis, septicemia or both. Serogroup W IMD has been increasing in prevalence in recent years, and observations suggest that it may present with atypical signs and symptoms. Herein, a literature search was performed to identify trends in atypical serogroup W IMD presentation in order to review those that are most prevalent. Findings indicate that the most prevalent atypical presentations of serogroup W IMD include acute gastrointestinal (GI) symptoms, septic arthritis and bacteremic pneumonia or severe upper respiratory tract infection, notably epiglottitis. Atypical clinical presentation is associated with higher case fatality rates and can lead to misdiagnoses. Such risks highlight the need for clinicians to consider IMD in their differential diagnoses of patients with acute GI symptoms, septic arthritis or bacteremic pneumonia, primarily in regions where serogroup W is prevalent.

First statewide meningococcal B vaccine program in infants, children and adolescents: evidence for implementation in South Australia.

Invasive meningococcal disease (IMD) is an uncommon but life-threatening infection caused by Neisseria meningitidis. Serogroups B, C, W and Y cause most IMD cases in Australia. The highest incidence occurs in children under 5 years of age. A second peak occurs in adolescents and young adults, which is also the age of highest carriage prevalence of N. meningitidis. Meningococcal serogroup B (MenB) disease predominated nationally before 2016 and has remained the predominant cause of IMD in South Australia with 82% of cases, compared with 35% in New South Wales, 35% in Queensland, 9% in Victoria, 29% in Western Australia and 36% nationally in 2016. MenB vaccination is recommended by the Australian Technical Advisory Group on Immunisation for infants up to 2 years of age and adolescents aged 15-19 years (age 15-24 years for at-risk groups, such as people living in close quarters or smokers), laboratory workers with exposure to N. meningitidis, and Aboriginal and Torres Strait Islander children from age 2 months to 19 years. Due to the epidemiology and disease burden from MenB, a meningococcal B vaccine program has been implemented in South Australia for individuals with age-specific incidence rates higher than the mean rate of 2.8/100 000 population in South Australia in the period 2000-2017, including infants, young children (< 4 years) and adolescents (15-20 years). Program evaluation of vaccine effectiveness against IMD is important. As observational evidence also suggests 4CMenB may have an impact on Neisseria gonorrhoeae with genetic homology between bacterial species, the vaccine impact on gonorrhoea will also be assessed.

A diagnostic challenge in clinical laboratory: Misidentification of Neisseria subflava as Neisseria meningitidis by MALDI-TOF MS.

MALDI-TOF MS provides fast, easy to perform and cost-effective diagnosis in clinical microbiology laboratories, however in some cases results of MALDI-TOF MS should be confirmed with additional tests. This confirmation is especially important for causes of life-threatening infections like Neisseria meningitidis. In our laboratory, three isolates were identified as N. meningitidis by Bruker MALDI Biotyper (BD, USA) between April 2018 and March 2019 from clinical specimens of blood, sputum, and urine. 16S rRNA sequencing was performed for further investigation. Two of the isolates were identified as Neisseria subflava and only one was confirmed as N. meningitidis by sequencing. These results show that MALDI-TOF MS is not always reliable in the diagnosis of N. meningitidis and clinical microbiologists should confirm these results with additional tests. Also, clinical correlations should be determined. Accurate identification of this microorganism is very important because of the necessity of prophylactic antimicrobial usage and biosafety precautions. Enlarged databases of Neisseria species are needed to overcome this problem.

Epidemiology and antibiotic resistance profile of bacterial meningitis in Morocco from 2015 to 2018.

Over a 4-year study period from 2015 to 2018, altogether 183 isolates of bacterial meningitis were collected from 12 hospitals covering the entire Moroccan territory. Neisseria meningitidis represented 58.5%, Streptococcus pneumoniae 35.5%, and Haemophilus influenzae type b 6%. H. influenzae type b mainly affected 5-year-olds and unvaccinated adults. N. meningitidis serogroup B represented 90.7% followed by serogroup W135 with 6.5%. Decreased susceptibility to penicillin G (DSPG) for all isolates accounted for 15.7%, with 11.6% being resistant to penicillin G (PG) and 4.1% decreased susceptibility. Cumulative results of all strains showed 2.7% decreased susceptibility to amoxicillin and 3.3% resistant, 2.2% of isolates were resistant to third-generation cephalosporin and 2.2% were decreased susceptible, 5.5% were resistant to chloramphenicol and 2.7% were resistant to rifampin. The frequency of DSPG observed in our study is more common in S. pneumoniae than in N. meningitidis (P < 0.05). These isolates have been found to be highly susceptible to antibiotics used for treatment and prophylaxis chemotherapy and the observed resistance remains rare. The impact of introduction of conjugate vaccines against H. influenzae type b and S. pneumoniae (PCVs) is an advantage in reducing meningitis cases due to these two species.

Detection of the United States Neisseria meningitidis urethritis clade in the United Kingdom, August and December 2019 - emergence of multiple antibiotic resistance calls for vigilance.

Since 2015 in the United States (US), the US Neisseria meningitidis urethritis clade (US_NmUC) has caused a large multistate outbreak of urethritis among heterosexual males. Its 'parent' strain caused numerous outbreaks of invasive meningococcal disease among men who have sex with men in Europe and North America. We highlight the arrival and dissemination of US_NmUC in the United Kingdom and the emergence of multiple antibiotic resistance. Surveillance systems should be developed that include anogenital meningococci.

Epidemiology of invasive meningococcal disease in Cyprus 2004 to 2018.

BackgroundDespite progress in the management of invasive meningococcal disease (IMD) it causes significant mortality and sequelae.AimThis study aims to describe the epidemiology and clinical characteristics of IMD in Cyprus and discuss the current immunisation programmes.MethodsThis is a retrospective study of all cases of IMD notified to the Ministry of Health between 2004 and 2018. Demographic, epidemiological, clinical and microbiological data were collected when a new case was notified. Risk factors associated with mortality were investigated using univariable logistic regression.Results54 cases of IMD were recorded, an overall incidence of 0.4 cases per 100,000 population. The incidence rate was highest among infants (7.2/100,000) and adolescents (1.4/100,000). Case fatality rate was 10.4%. Serogroup B accounted for 24 of 40 cases caused by known serogroup. Serogroups W and Y comprised nine cases and were responsible for most fatal cases. Serogroup C was the cause in only four cases. There was an increase in the odds of death with increasing age, while the presence of meningitis in the clinical picture was found to be associated with lower odds of death.ConclusionDespite the low incidence of IMD in Cyprus, it remains an important cause of morbidity and mortality. Serogroup B is the most frequent serogroup, while incidence of serogroups W and Y is rising. Monitoring new cases and yearly evaluation of the immunisation programmes by the National Immunization Technical Advisory Group (NITAG) is essential for successful control of the disease.

[Meningococcemia: Different Serotypes in the Same Region]. / Meningokoksemi: Ayni Cografyada Farkli Serotipler.

Meningococcal infections are important health problems causing high morbidity and mortality. Neisseria meningitidis have 13 serogroups. A, B, C, Y and W135 are the most common causes of invasive disease among those serogroups. The distribution of the serogroups differs according to the geographical regions and the age groups. In this case report, two cases of meningococcemia infected with serogroup C and Y of N.meningitidis rarely seen in our country were presented. First case was a two and a half year-old female patient who has admitted to our pediatric emergency unit with fever and rash spreading from lower extremities to her body. The patient had diffuse purpuric rash with generalized weakness and tendency to sleep at admission. The patient has been suspected as meningococcemia because of the skin rash, tendency to sleep and hypotension. Antibiotics treatment was started immediately and lumber puncture was performed. In blood tests, leukocyte count: 3600/mm3 (61% neutrophils), hemoglobin: 11.1 g/ dl, platelet count: 127.000/mm3 , C-reactive protein: 10 mg/dl, erythrocyte sedimentation rate: 6 mm/ hour, prothrombin time: 28.8 seconds (normal value= 11-16), prothrombin activity: 36%, international normalized ratio (INR): 2.13 (normal value= 1-1.5), activated partial thromboplastin time: 57.7 seconds (normal value= 25-35 sec), fibrinogen: 246 mg/dl (normal value= 200-400 mg/dl) and in cerebrospinal fluid protein: 21 mg/dl and glucose: 62 mg/dl were found. There were eight cells in the microscopic examination. Skin rashes were increased and the patient became hypotensive. No microorganisms were isolated in blood and cerebrospinal cultures. N.meningitidis serogroup C was isolated from the cerebrospinal fluid of the patient using polymerase chain reaction (PCR). The patient suffered from immune-mediated arthritis in the sixth day of treatment and nonsteroidal anti-inflammatory drugs were given. The patient has recovered with antibiotics, fresh frozen plasma and inotropic treatment. Second case was a 13 year-old male patient who has admitted three days after the first case with a pre-diagnosis of malignancy because of pancytopenia and fever. The patient had generalized weakness and a few petechial purpuric rashes at the facial region at admission. After the admission general status of the patient has worsened rapidly and he has died as a result of cardiovascular arrest. Blood tests in admission showed leukocyte count: 6000/mm3 (79% neutrophils), hemoglobin: 17.3 mg/dl, platelet count: 16.000/mm3 , C-reactive protein: 8.63 mg/dl, prothrombin time: 92.6 seconds, prothrombin activity: 10%, INR: 6.78, activated partial thromboplastin time: 231.5 seconds. Cerebrospinal fluid obtained from postmortem lumbar puncture showed no growth (protein: 95 mg/dl, glucose: 35 mg/dl) and N.meningitidis serogroup Y was detected by PCR. Two meningococcemia cases caused by two different serogroups which are rarely seen in our region in recent years were presented at the same time period in the same hospital. This case report pointed out that surveillance has a great importance in such diseases.

[Neisseria meningitidis isolated from patients in men who have sex with men]. / Neisseria meningitidis aislada de muestras de hombres que tienen sexo con hombres.

During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5µg/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.

Invasive Meningococcal Disease in Africa's Meningitis Belt: More Than Just Meningitis?

Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa's meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization's updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa's meningitis belt, will enhance meningococcal disease prevention across the belt.

Toward a Global Genomic Epidemiology of Meningococcal Disease.

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.