Variation in CFHR3 determines susceptibility to meningococcal disease by controlling factor H concentrations.

Neisseria meningitidis protects itself from complement-mediated killing by binding complement factor H (FH). Previous studies associated susceptibility to meningococcal disease (MD) with variation in CFH, but the causal variants and underlying mechanism remained unknown. Here we attempted to define the association more accurately by sequencing the CFH-CFHR locus and imputing missing genotypes in previously obtained GWAS datasets of MD-affected individuals of European ancestry and matched controls. We identified a CFHR3 SNP that provides protection from MD (rs75703017, p value = 1.1 × 10-16) by decreasing the concentration of FH in the blood (p value = 1.4 × 10-11). We subsequently used dual-luciferase studies and CRISPR gene editing to establish that deletion of rs75703017 increased FH expression in hepatocyte by preventing promotor inhibition. Our data suggest that reduced concentrations of FH in the blood confer protection from MD; with reduced access to FH, N. meningitidis is less able to shield itself from complement-mediated killing.

Genomic diversity and antimicrobial susceptibility of invasive Neisseria meningitidis in South Africa, 2016-2021.

BACKGROUND: Invasive meningococcal isolates in South Africa have in previous years (<2008) been characterized by serogroup B, C, W and Y lineages over time, with penicillin intermediate resistance (peni) at 6%. We describe the population structure and genomic markers of peni among invasive meningococcal isolates in South Africa, 2016-2021. METHODS: Meningococcal isolates were collected through national, laboratory-based invasive meningococcal disease (IMD) surveillance. Phenotypic antimicrobial susceptibility testing and whole-genome sequencing were performed, and the mechanism of reduced penicillin susceptibility was assessed in silico. RESULTS: Of 585 IMD cases reported during the study period, culture and PCR-based capsular group was determined for 477/585 (82%); and 241/477 (51%) were sequenced. Predominant serogroups included NmB (210/477; 44%), NmW (116/477; 24%), NmY (96/477; 20%) and NmC (48/477; 10%). Predominant clonal complexes (CC) were CC41/44 in NmB (27/113; 24%), CC11 in NmW (46/56; 82%), CC167 in NmY (23/44; 53%), and CC865 in NmC (9/24; 38%). Peni was detected in 16% (42/262) of isolates, and was due to the presence of a penA mosaic, with the majority harboring penA7, penA9 or penA14. CONCLUSION: IMD lineages circulating in South Africa were consistent with those circulating prior to 2008, however peni was higher than previously reported, and occurred in a variety of lineages.

Impact of Meningococcal ACWY Vaccination Program during 2017-18 Epidemic, Western Australia, Australia.

The rising incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W in Western Australia, Australia, presents challenges for prevention. We assessed the effects of a quadrivalent meningococcal vaccination program using 2012-2020 IMD notification data. Notification rates peaked at 1.8/100,000 population in 2017; rates among Aboriginal and Torres Strait Islander populations were 7 times higher than for other populations. Serogroup W disease exhibited atypical manifestations and increased severity. Of 216 cases, 20 IMD-related deaths occurred; most (19/20) were in unvaccinated persons. After the 2017-2018 targeted vaccination program, notification rates decreased from 1.6/100,000 population in 2018 to 0.9/100,000 population in 2019 and continued to decline in 2020. Vaccine effectiveness (in the 1-4 years age group) using the screening method was 93.6% (95% CI 50.1%-99.2%) in 2018 and 92.5% (95% CI 28.2%-99.2%) in 2019. Strategic planning and prompt implementation of targeted vaccination programs effectively reduce IMD.

Serogroup B Invasive Meningococcal Disease in Older Adults Identified by Genomic Surveillance, England, 2022-2023.

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Concurrent Outbreaks of Hepatitis A, Invasive Meningococcal Disease, and Mpox, Florida, USA, 2021-2022.

In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March--June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Obstetric and Neonatal Invasive Meningococcal Disease Caused by Neisseria meningitidis Serogroup W, Western Australia, Australia.

Three mother-baby pairs with invasive meningococcal disease occurred over 7 months in Western Australia, Australia, at a time when serogroup W sequence type 11 clonal complex was the predominant local strain. One mother and 2 neonates died, highlighting the role of this strain as a cause of obstetric and early neonatal death.

Propositive follow-up: Long-term immune responses to the 4CMenB and MenACWY vaccines in people living with HIV.

BACKGROUND: People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination. METHODS: Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300). RESULTS: A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%). CONCLUSIONS: Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups.

PCR-positive meningococcal CSF infection without pleocytosis but high IL-6 and IL-8.

BACKGROUND: Meningococcal meningitis is still a severe disease causing high mortality and morbidity rates. Early diagnosis is crucial to ensure prompt antibiotic therapy. However, identification of the pathogen can be challenging. CASE PRESENTATION: A 32-year-old male patient with systemic lupus erythematosus (SLE) presented to the emergency room with fever, nausea, vomiting, headache and lower back pain as well as multiple petechial bleedings. On suspicion of meningococcal infection, the emergency doctor had already administered one dose of ceftriaxone before arrival to the clinic. Blood works showed massive inflammation due to bacterial infection. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and glucose levels but PCR was positive for Neisseria meningitis and IL-6 as well as IL-8 were elevated. On antibiotic therapy with ceftriaxone, the patient's condition improved quickly. CONCLUSIONS: We present a rare case of meningococcal infection of the CSF in a SLE patient without further CSF abnormalities. We discuss the involvement of early antibiotic treatment and the role of the patient's immune status in the normal CSF findings of this case. Moreover, this case demonstrates the importance of early antibiotic therapy in bacterial meningitis for the clinical outcome.

Geographical distribution of invasive meningococcal disease and carriage: A spatial analysis.

Little information exists concerning the spatial relationship between invasive meningococcal disease (IMD) cases and Neisseria meningitidis (N. meningitidis) carriage. The aim of this study was to examine whether there is a relationship between IMD and asymptomatic oropharyngeal carriage of meningococci by spatial analysis to identify the distribution and patterns of cases and carriage in South Australia (SA). Carriage data geocoded to participants' residential addresses and meningococcal case notifications using Postal Area (POA) centroids were used to analyse spatial distribution by disease- and non-disease-associated genogroups, as well as overall from 2017 to 2020. The majority of IMD cases were genogroup B with the overall highest incidence of cases reported in infants, young children, and adolescents. We found no clear spatial association between N. meningitidis carriage and IMD cases. However, analyses using carriage and case genogroups showed differences in the spatial distribution between metropolitan and regional areas. Regional areas had a higher rate of IMD cases and carriage prevalence. While no clear relationship between cases and carriage was evident in the spatial analysis, the higher rates of both carriage and disease in regional areas highlight the need to maintain high vaccine coverage outside of the well-resourced metropolitan area.

Follow-up care experience of patients with invasive meningococcal disease and their family caregivers: a qualitative study.

BACKGROUND: Clinical guidelines recommend systematic follow-up of patients surviving invasive meningococcal disease (IMD) to assess sequelae. However, little is known about survivors and family caregivers' experiences of the follow-up care. Study sought to explore IMD survivors' and their family caregivers' experiences after hospitalization for IMD and to identify unmet needs. METHODS: Semi-structured interviews were conducted with patients and family caregivers, identified through hospitals database. Interviews were audiotaped, transcribed and subject to a thematic analysis. NVivo software was used for data management and analysis. RESULTS: Eight IMD survivors and 14 family caregivers were interviewed. Three themes were identified from the data: (1) perception of patient and family caregiver on follow-up after IMD and role of healthcare professionals; (2) access to care and support; (3) relationship with healthcare professionals. Although most were satisfied with follow-up care after IMD, suggestions for improving the healthcare pathway were made relating information on potential sequelae and follow-up care, coordination, and access to psychological support. CONCLUSIONS: This study confirms the need for more structured follow-up care for patients suffering from IMD and their families which is currently limited and focused on physical recovery. Optimal follow-up should aim to provide sufficient information, emotional support and logistical support for patient and family caregivers. TRIAL REGISTRATION: Ethics Committee of University of Lyon, France (ref: 2022-06-23-002).

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.

An isothermal CRISPR- based lateral flow assay for detection of Neisseria meningitidis.

BACKGROUND: Neisseria meningitidis can cause life-threatening meningococcal meningitis and meningococcemia. Old standard microbiological results from CSF/blood cultures are time consuming. This study aimed to combine the sensitivity of loop-mediated isothermal nucleic acid amplification (LAMP) with the specificity of CRISPR/Cas12a cleavage to demonstrate a reliable diagnostic assay for rapid detection of N. meningitidis. METHODS: A total of n = 139 samples were collected from patients with suspected meningococcal disease and were used for evaluation. The extracted DNA was subjected to qualitative real-time PCR, targeting capsular transporter gene (ctrA) of N. meningitidis. LAMP-specific primer pairs, also targeting the ctrA, were designed and the LAMP products were subjected to CRISPR/Cas12 cleavage reaction. the readout was on a lateral flow strip. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LAMP-CRISPR/Cas was compared with real-time PCR assays. The limit of detection (LOD) was established with serial dilutions of the target N. meningitidis DNA and calculated by Probit regression analysis. RESULTS: Six LAMP assay-specific primers were developed targeting the ctrA gene of N. meningitidis, which is conserved in all meningococcal serogroups. The LAMP primers did not amplify DNA from other bacterial DNA tested, showing 100% specificity. The use of 0.4 M betaine increased the sensitivity and stability of the reaction. LAMP-CRISPR/Cas detected meningococcal serogroups (B, C, W). The assay showed no cross-reactivity and was specific for N. meningitidis. The LOD was 74 (95% CI: 47-311) N. meningitidis copies. The LAMP-CRISPR/Cas performed well compared to the gold standard. In the 139 samples from suspected patients, the sensitivity and specificity of the test were 91% and 99% respectively. CONCLUSION: This developed and optimized method can complement for the available gold standard for the timely diagnosis of meningococcal meningitis and meningococcemia.

Public health management of invasive meningococcal disease outbreaks: worldwide 1973-2018, a systematic review.

BACKGROUND: Infectious disease outbreaks are an ongoing public health concern, requiring extensive resources to prevent and manage. Invasive Meningococcal Disease (IMD) is a severe outcome of infection with Neisseria meningitidis bacteria, which can be carried and transmitted asymptomatically. IMD is not completely vaccine-preventable, presenting an ongoing risk of outbreak development. This review provides a retrospective assessment of public health management of IMD outbreaks. METHODS: A systematic search was performed in PubMed and EMBASE. English-language studies reporting on IMD outbreaks and associated public health response were considered eligible. Reporting on key characteristics including outbreak size, duration, location, and public health response were assessed against Strengthening the Reporting of Observational studies in Epidemiology guidelines. A summary of lessons learned and author recommendations for each article were also discussed. RESULTS: 39 eligible studies were identified, describing 35 outbreaks in seven regions. Responses to outbreaks were mostly reactive, involving whole communities over prioritising those at highest risk of transmission. Recent responses identified a need for more proactive and targeted controls. Reporting was inconsistent, with key characteristics such as outbreak size, duration, or response absent or incompletely described. CONCLUSION: There is a need for clear, comprehensive reporting on IMD outbreaks and their public health response to inform policy and practice for subsequent outbreaks of IMD and other infectious diseases.

The impact of regional disparities on the availability of meningococcal vaccines in the US.

BACKGROUND: In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC's Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies. METHODS: The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC's Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC's Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines. RESULTS: After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates. CONCLUSIONS: Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.

Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California.

BACKGROUND: Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS: We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS: The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34-.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82-1.17). CONCLUSIONS: These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004-2020.

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Maori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Maori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Detection of Novel US Neisseria meningitidis Urethritis Clade Subtypes in Japan.

Neisseria meningitidis causes invasive meningococcal diseases and has also been identified as a causative agent of sexually transmitted infections, including urethritis. Unencapsulated sequence type 11 meningococci containing the gonococcal aniA-norB locus and belonging to the United States N. meningitidis urethritis clade (US_NmUC) are causative agents of urethral infections in the United States, predominantly among men who have sex with men. We identified 2 subtypes of unencapsulated sequence type 11 meningococci in Japan that were phylogenetically close to US_NmUC, designated as the Japan N. meningitidis urethritis clade (J_NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US_NmUC and J_NmUS urethritis-associated meningococci is disseminated worldwide. Global monitoring of urethritis-associated N. meningitidis isolates should be performed to further characterize microbiologic and epidemiologic characteristics of urethritis clade meningococci.

The propositive study: Immunogenicity and safety of a four-component recombinant protein-based vaccine against MenB and a quadrivalent conjugate MenACWY vaccine in people living with HIV.

BACKGROUND: People living with HIV have been shown to have an increased risk of invasive meningococcal disease. In some countries, meningococcal vaccines are now routinely recommended to all people living with HIV, but no study has yet assessed the immunogenicity and safety of a meningococcal serogroup B vaccine or the co-administration of a MenB and MenACWY vaccine in people living with HIV. METHODS: This phase IV open-label clinical trial investigated the immunogenicity and safety of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in a population of people living with HIV. Immunogenicity analysis was performed before vaccination and 1 month after the second doses of 4CMenB and MenACWY. Primary outcome measures were serum bactericidal assay geometric mean titres against three MenB reference strains at baseline and 1 month post vaccination, the proportion of participants achieving a putative protective titre of ≥4, and the proportion of participants with a ≥4-fold rise in titre from baseline. Secondary outcome measures were serum bactericidal assay geometric mean titres against MenA, C, W, and Y reference strains at baseline and 1 month post vaccination, the proportion achieving a putative protective titre of ≥8, and the proportion with a ≥4-fold rise in titre from baseline. Safety outcomes were solicited and unsolicited adverse events in the 7 days following vaccination. The trial was registered with clinicaltrials.gov (NCT03682939). FINDINGS: In total, 55 participants aged 20-45 years were enrolled. All participants (100%; 95% confidence interval [CI] 93-100) achieved putative protective titres for two of the three MenB strains and for MenA, W, and Y. A total of 98% (95% CI 89-100) achieved a protective titre for the third MenB strain and 94% (95% CI 83-99) for MenC. No serious adverse events were reported. INTERPRETATION: 4CMenB and MenACWY were immunogenic and well-tolerated in a population of people living with HIV 1 month after two doses.

Molecular characteristics of Neisseria meningitidis carriage strains in university students in Lithuania.

BACKGROUND: Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of invasive meningococcal disease (IMD). No carriage studies have been performed among the general population in Lithuania, whereas the incidence of IMD in Lithuania was among the highest in European countries from 2009 to 2019. RESULTS: We analyzed a total of 401 oropharyngeal samples collected from university students from December 2021 to February 2023 for N. meningitidis carriage using direct swab PCR assays and culture. The overall carriage prevalence based on both or either swab PCR or culture was 4.99%. PCR-based assays were used to characterize 15 carriage isolates, including detection of genogroup, multilocus sequence typing profile, and typing of antigens PorA and FetA. The most common carriage isolates were capsule null locus (cnl), accounting for 46.7%, followed by genogroups B (26.7%) and Y (13.3%). We also performed a molecular characterization of invasive N. meningitidis isolates collected during the COVID-19 pandemic and post-pandemic period to understand better the meningococcal carriage in the context of prevailing invasive strains. Despite the substantial decrease in the incidence of IMD during the 2020-2022 period, clonal complex 32 (CC32) of serogroup B continued to be the most prevalent IMD-causing CC in Lithuania. However, CC32 was not detected among carriage isolates. The most common CCs were CC269, CC198, and CC1136. The antigen peptide variants found in most carried isolates were classified as 'insufficient data' according to the MenDeVAR Index to evaluate the potential coverage by the 4CMenB vaccine. Nearly half of the isolates were potentially covered by the Men-Fhbp vaccine. Resistance to ciprofloxacin was detected only for one cnl isolate. All isolates were susceptible to penicillin and ceftriaxone. Our analysis identified frequent partying (≥ 4 times/month) as a risk factor for meningococcal carriage, whereas smoking, living in a dormitory, and previous COVID-19 illness were not associated with the carriage. CONCLUSIONS: Our study revealed a low prevalence of meningococcal carriage among university students in Lithuania. The carriage isolates showed genetic diversity, although almost half of them were identified as having a null capsule locus.

Antibiotics modulates the virulence of Neisseria meningitidis by regulating capsule synthesis.

The opportunistic pathogens residing are frequently exposed to range of antimicrobials which affects virulence attributes. Neisseria meningitidis, is a host-restricted commensal of human upper respiratory tract which is subjected to a variety of stresses within the host, including antibiotic exposure. One of the most important virulence factors for pathogenesis is the meningococcal lipo-oligosaccharide capsule. Role of capsules in antimicrobial resistance and persistence is not yet established. In this study, different virulence factors of N. meningitidis were examined in presence of sub-MIC of four antibiotics: penicillin, ciprofloxacin, erythromycin and chloramphenicol. We observed increased production of the capsule by N. meningitidis when grown in the presence of penicillin, erythromycin, and chloramphenicol at sub-inhibitory concentration. Capsular production increase concurrently with increased resistance to inducing antibiotic which also confers increased survival in human serum. Finally, we show that increased capsule production in response to antibiotic exposure is aided by siaC, ctrB, lipA gene expression. These findings show that capsule synthesis, a major pathogenicity determinant, is regulated in response to antibiotic stress. Our findings support a model in which gene expression changes caused by ineffective antibiotic treatment cause N. meningitidis transition between states of low and high virulence potential, contributing to pathogen's opportunistic nature.