Investigation and response to an outbreak of Neisseria meningitidis serogroup Y ST-1466 urogenital infections, Australia.

Abstract: In 2023, an increased number of urogenital and anorectal infections with Neisseria meningitis serogroup Y (MenY) were reported in New South Wales (NSW). Whole genome sequencing (WGS) found a common sequence type (ST-1466), with limited sequence diversity. Confirmed outbreak cases were NSW residents with a N. meningitidis isolate matching the cluster sequence type; probable cases were NSW residents with MenY isolated from a urogenital or anorectal site from 1 July 2023 without WGS testing. Of the 41 cases, most were men (n = 27), of whom six reported recent contact with a female sex worker. Five cases were men who have sex with men and two were female sex workers. Laboratory alerts regarding the outbreak were sent to all Australian jurisdictions through the laboratories in the National Neisseria Network. Two additional states identified urogenital MenY ST-1466 infections detected in late 2023. Genomic analysis showed all MenY ST-1466 sequences were interspersed, suggestive of an Australia-wide outbreak. The incidence of these infections remains unknown, due to varied testing and reporting practices both within and across jurisdictions. Isolates causing invasive meningococcal disease (IMD) in Australia are typed, and there has been no MenY ST-1466 IMD recorded in Australia to end of March 2024. Concerns remain regarding the risk of IMD, given the similarity of these sequences with a MenY ST-1466 IMD strain causing a concurrent outbreak in the United States of America.

Multicentre double-blind randomised placebo-controlled trial evaluating the efficacy of the meningococcal B vaccine, 4CMenB (Bexsero), against Neisseria gonorrhoeae infection in men who have sex with men: the GoGoVax study protocol.

INTRODUCTION: Gonorrhoea, the sexually transmissible infection caused by Neisseria gonorrhoeae, has a substantial impact on sexual and reproductive health globally with an estimated 82 million new infections each year worldwide. N. gonorrhoeae antimicrobial resistance continues to escalate, and disease control is largely reliant on effective therapy as there is no proven effective gonococcal vaccine available. However, there is increasing evidence from observational cohort studies that the serogroup B meningococcal vaccine four-component meningitis B vaccine (4CMenB) (Bexsero), licensed to prevent invasive disease caused by Neisseria meningitidis, may provide cross-protection against the closely related bacterium N. gonorrhoeae. This study will evaluate the efficacy of 4CMenB against N. gonorrhoeae infection in men (cis and trans), transwomen and non-binary people who have sex with men (hereafter referred to as GBM+). METHODS AND ANALYSIS: This is a double-blind, randomised placebo-controlled trial in GBM+, either HIV-negative on pre-exposure prophylaxis against HIV or living with HIV (CD4 count >350 cells/mm3), who have had a diagnosis of gonorrhoea or infectious syphilis in the last 18 months (a key characteristic associated with a high risk of N. gonorrhoeae infection). Participants are randomised 1:1 to receive two doses of 4CMenB or placebo 3 months apart. Participants have 3-monthly visits over 24 months, which include testing for N. gonorrhoeae and other sexually transmissible infections, collection of demographics, sexual behaviour risks and antibiotic use, and collection of research samples for analysis of N. gonorrhoeae-specific systemic and mucosal immune responses. The primary outcome is the incidence of the first episode of N. gonorrhoeae infection, as determined by nucleic acid amplification tests, post month 4. Additional outcomes consider the incidence of symptomatic or asymptomatic N. gonorrhoeae infection at different anatomical sites (ie, urogenital, anorectum or oropharynx), incidence by N. gonorrhoeae genotype and antimicrobial resistance phenotype, and level and functional activity of N. gonorrhoeae-specific antibodies. ETHICS AND DISSEMINATION: Ethical approval was obtained from the St Vincent's Hospital Human Research Ethics Committee, St Vincent's Hospital Sydney, NSW, Australia (ref: 2020/ETH01084). Results will be disseminated in peer-reviewed journals and via presentation at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04415424.

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.

The important lessons lurking in the history of meningococcal epidemiology.

INTRODUCTION: The epidemiology of invasive meningococcal disease (IMD), a rare but potentially fatal illness, is typically described as unpredictable and subject to sporadic outbreaks. AREAS COVERED: Meningococcal epidemiology and vaccine use during the last ~ 200 years are examined within the context of meningococcal characterization and classification to guide future IMD prevention efforts. EXPERT OPINION: Historical and contemporary data highlight the dynamic nature of meningococcal epidemiology, with continued emergence of hyperinvasive clones and affected regions. Recent shifts include global increases in serogroup W disease, meningococcal antimicrobial resistance (AMR), and meningococcal urethritis; additionally, unvaccinated populations have experienced disease resurgences following lifting of COVID-19 restrictions. Despite these changes, a close analysis of meningococcal epidemiology indicates consistent dominance of serogroups A, B, C, W, and Y and elevated IMD rates among infants and young children, adolescents/young adults, and older adults. Demonstrably effective vaccines against all 5 major disease-causing serogroups are available, and their prophylactic use represents a powerful weapon against IMD, including AMR. The World Health Organization's goal of defeating meningitis by the year 2030 demands broad protection against IMD, which in turn indicates an urgent need to expand meningococcal vaccination programs across major disease-causing serogroups and age-related risk groups.

Prevalence, serogroup distribution and risk factors of Neisseria meningitidis carriage in high school and university students in Hungary.

Neisseria meningitidis causes life-threatening invasive meningococcal disease (IMD) with high mortality worldwide. Asymptomatic pharyngeal meningococcus colonisation is an important reservoir for the spread of the bacterium. The aim of this study was to determine N. meningitidis colonisation rates in asymptomatic high school and university students and to identify risk factors for carriage. Oropharyngeal swab samples and data from a self-reported questionnaire were obtained from overall 610 students, among them 303 university students and 307 high school students, aged between 15 and 31 years in Budapest, Hungary, between November 2017 and December 2018. Meningococcal carriage and serogroup of N. meningitidis were determined by RT-PCR from DNA extracted directly from the specimen. N. meningitidis was identified in 212 (34.8 %) of the participants. Significantly higher carriage rate was found among high school students (48.9 %) compared to university students (20.5 %). Peak of colonisation rate was among 17-19-year-old students (48.7 %). Most carriage isolates were non-typable (87.3 %). From the 212 meningococcus carriers, 19 were colonised by serogroup B (9 %), 5 by serogroup C (2.4 %), and 1 had serogroup Y (0.5 %). Significantly higher colonisation rate was found among males (42.4 %) than in females (33.1 %). Antibiotic use in the past 2 months has decreased the rate of meningococcal colonisation. Recent respiratory infection, active or passive smoking and attending parties have not influenced meningococcal colonisation rate significantly. In conclusion, we have found high asymptomatic meningococcus carriage rate among high school students and young adults, however, the majority of the colonizing meningococci were non-typable.

Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance - United States, 2024.

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts. Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin. Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased. Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure. Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains. Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin. Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.

Cost-effectiveness analysis of vaccination strategies against meningococcal disease for children under nine years of age in China.

Meningococcal vaccination strategies in China are intricate, including multiple vaccines targeting different serogroups. The current National Immunization Program (NIP) includes two polysaccharide vaccines for serogroups A and C (MPV-A and MPV-AC), covering limited serogroups and requiring adaptation. This study aims to evaluate the cost-effectiveness of replacing the current strategy with alternative strategies utilizing non-NIP vaccines to inform policy decisions. From a societal perspective, a decision tree-Markov model was constructed to simulate the economic and health consequences of meningococcal disease in a 2019 birth cohort with four vaccination strategies. Epidemiology, vaccine efficacy, cost, and other parameters were derived from previous studies. We conducted sensitivity analyses to assess the robustness of the findings and explored prices for non-NIP vaccines that enable cost-effective strategies. Compared to the current strategy, alternative strategies using quadrivalent polysaccharide vaccine (MPV-4), bivalent conjugate vaccine (MCV-AC), and quadrivalent conjugate vaccine (MCV-4) could avoid 91, 286, and 455 more meningococcal cases. The ICERs were estimated at approximately $250 thousand/QALY, $450 thousand/QALY, and $1.5 million/QALY, all exceeding the threshold of three times GDP per capita. The alternative strategies were not cost-effective. However, if vaccine prices were reduced to $3.9 for MPV-4, $9.9 for MCV-AC, and $12 for MCV-4, the corresponding strategy would be cost-effective. The current meningococcal vaccination strategy in China could effectively prevent the disease at a low cost, but with limited serogroup coverage. Strategies using MPV-4, MCV-AC, or MCV-4 could increase health benefits at a substantial cost, and might become cost-effective if vaccine prices decrease.

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.

Invasive meningococcal disease in South-Eastern European countries: Do we need to revise vaccination strategies?

Invasive meningococcal disease (IMD) is an acute life-threatening infection caused by the gram-negative bacterium, Neisseria meningitidis. Globally, there are approximately half a million cases of IMD each year, with incidence varying across geographical regions. Vaccination has proven to be successful against IMD, as part of controlling outbreaks, and when incorporated into national immunization programs. The South-Eastern Europe Meningococcal Advocacy Group (including representatives from Croatia, the Czech Republic, Greece, Hungary, Poland, Romania, Serbia, Slovenia and Ukraine) was formed in order to discuss the potential challenges of IMD faced in the region. The incidence of IMD across Europe has been relatively low over the past decade; of the countries that came together for the South-Eastern Meningococcal Advocacy Group, the notification rates were lower than the European average for some country. The age distribution of IMD cases was highest in infants and children, and most countries also had a further peak in adolescents and young adults. Across the nine included countries between 2010 and 2020, the largest contributors to IMD were serogroups B and C; however, each individual country had distinct patterns for serogroup distribution. Along with the variations in epidemiology of IMD between the included countries, vaccination policies also differ.

[Out-of-hours General Practice: a case-report about Neisseria meningitidis in the health district of Grado (Gorizia), Italy.] / Continuità assistenziale: un case-report su Neisseria meningitidis nel distretto sanitario di Grado (Gorizia).

Neisseria meningitidis causes life-threatening invasive diseases, such as sepsis, pneumonia, and meningitis. In Italy, as in many other countries, despite vaccination programs, the misdiagnosis of meningococcal infections and the persistence of vaccination hesitancy and of unvaccinated people can lead to possible epidemics. Following the CARE Guidelines, this case-report describes a young woman presented with fever and a strange rash to the General Practice out-of-hours in the island of Grado (Gorizia - Italy), lately recognized as Neisseria meningitidis infection. After a prompt evaluation, she was referred to a central hospital for correct diagnosis and treatment. Study and management of the case and its close-contacts was also carried out by the Prevention Department to provide prophylaxis. The Italian Ooh service is active every night, weekend and on holidays, representing an aid to limit improper access to the Emergency Department, but especially in rural areas, patients with urgent conditions also mainly go to the Ooh, first or alternatively to reach a hospital equipped with ER. The presented case underlines the fundamental role played by Ooh in the timely identification of a meningococcal infection in a patient presenting with non-neurological symptoms, making the correct referral to the specialist department of the nearest central hospital. It is essential to conduct a detailed medical history, even by telephone, and carry out a visit to evaluate the opportunity for hospital admission, especially to achieve early identification of life-threatening communicable diseases. It is also important that medical training, even after graduation, emphasizes the importance of maintaining awareness and making rapid recognition of the key symptoms of these conditions, although rare.

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.

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.

Longitudinal study of meningococcal carriage in adolescents and young adults in South Australia 2017-2020.

BACKGROUND: This analysis investigated longitudinal changes in meningococcal carriage in adolescents in South Australia over 4 years. METHODS: Data from the "B Part of It" study, which included a state-wide cluster randomized controlled trial in secondary-school students (n = 34,489 in 2017 and 2018) and serial cross-sectional studies in school leavers aged 17-25 years (n = 4028 in 2019-2020). Individuals had oropharyngeal swabs collected annually. This study included two unique cohorts: (1) individuals enrolled in 2019, with three consecutive annual swabs taken in 2017, 2018 and 2019; and (2) individuals enrolled in 2020, with swabs taken in 2017, 2018, and 2020. Disease-associated N. meningitidis genogroups were identified using PCR and whole genome sequencing. Univariate analysis identified risk factors for recurrent carriage (≥2). RESULTS: Among school leavers, 50 (1.7%, total n = 2980) had carriage detected at successive visits. In participants with meningococcal carriage at successive visits, 38/50 (76.0%) had the same genogroup detected by porA PCR. Of those, 19 had the same MLST type and demonstrated minimal variation, indicating they most likely had sustained carriage of the same isolate (range 226 to 490 days, mean duration 352 [SD 51] days). In the 2019 school leaver cohort, 6.7% acquired carriage in their first year out of school compared to 3.3% in their final school year. Compared to single carriage detection, recurrent carriage was potentially more likely in older adolescents (16 compared to ≤15 years; OR = 1.97 (95%CI 1.0, 3.86); p = 0.048). CONCLUSION: Whilst carriage is typically transient, some adolescents/young adults may have persistent carriage and are likely to be an important group in the transmission of meningococci.

Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative.

This review details recent findings from the Global Meningococcal Initiative's (GMI) recent meeting on the surveillance and control strategies for invasive meningococcal disease in the Middle East. The nature of case reporting and notification varies across the region, with many countries using bacterial meningitis as an IMD case definition in lieu of meningitis and septicaemia. This may overlook a significant burden associated with IMD leading to underreporting or misreporting of the disease. Based on these current definitions, IMD reported incidence remains low across the region, with historical outbreaks mainly occurring due to the Hajj and Umrah mass gatherings. The use of case confirmation techniques also varies in Middle Eastern countries. While typical microbiological techniques, such as culture and Gram staining, are widely used for characterisation, polymerase chain reaction (PCR) testing is utilised in a small number of countries. PCR testing may be inaccessible for several reasons including sample transportation, cost, or a lack of laboratory expertise. These barriers, not exclusive to PCR use, may impact surveillance systems more broadly. Another concern throughout the region is potentially widespread ciprofloxacin resistance since its use for chemoprophylaxis remains high in many countries.

CLINICAL AND EPIDEMIOLOGICAL FEATURES OF MENINGOCOCCAL INFECTION AND ITS EARLY DIAGNOSIS IN RESIDENTS OF THE TRANSCARPATHIAN REGION.

OBJECTIVE: The aim: To identify clinical and epidemiological features of meningococcal infection on the initial day of a patient's medical consultation, as well as the efficacy of laboratory examinations. PATIENTS AND METHODS: Materials and methods: A retrospective analysis of 76 patients' histories diagnosed with meningococcal disease was carried out. CONCLUSION: Conclusions: Patients in the Transcarpathian region mainly develop an atypical form of meningococcal disease. Only half of all patients diagnosed with meningococcemia had a classical hemorrhagic rash. Generalized forms of meningococcal disease may proceed with normal or subfebrile temperature and without severe leukocytosis. We doubt the use of bacteriological methods of laboratory diagnosis due to their low effectiveness. The most sensitive method of laboratory diagnosis is a microscopic examination of blood smear, and cerebrospinal fluid.

Informing the use of a supplementary immunisation programme for the management of a community cluster of invasive meningococcal disease, Yorkshire, 2022.

OBJECTIVES: To outline the management of a community cluster of serogroup B invasive meningococcal disease (IMD) cases, including key factors for decision making and the choice and implementation of control measures. STUDY DESIGN: Descriptive report of cluster management. METHODS: Subtyping of IMD cases identified a number of potentially linked cases in a defined geographical area. An Incident Management Team (IMT) was convened to coordinate the public health response. A case definition was developed in order to identify further cases within the cluster. RESULTS: Four cases of IMD met the case definition and were initially considered as part of this cluster. Three resided in the same small town, which was the focus for public health management. The IMT agreed that it would be proportionate to instigate additional control measures. The population at higher risk of infection were identified, and a supplementary vaccination programme was rolled out in the community. Over five clinics, 45.6% (639/1401) of the target cohort received at least one dose of the vaccine, with 34.7% (486/1401) receiving both doses. Inequalities in uptake were observed by sex, age and deprivation. CONCLUSIONS: Decision making for public health responses to IMD clusters is complex. Informed by epidemiological evidence, numerous partners engaged in collaborative decision making, which was critical for the effective implementation of the community response. Links between the local authority public health team and the community enabled the use of existing structures and relationships to maximise the number of vaccinations delivered. No further cases of IMD linked to this cluster were identified.

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.

Inference of transmission dynamics and retrospective forecast of invasive meningococcal disease.

The pathogenic bacteria Neisseria meningitidis, which causes invasive meningococcal disease (IMD), predominantly colonizes humans asymptomatically; however, invasive disease occurs in a small proportion of the population. Here, we explore the seasonality of IMD and develop and validate a suite of models for simulating and forecasting disease outcomes in the United States. We combine the models into multi-model ensembles (MME) based on the past performance of the individual models, as well as a naive equally weighted aggregation, and compare the retrospective forecast performance over a six-month forecast horizon. Deployment of the complete vaccination regimen, introduced in 2011, coincided with a change in the periodicity of IMD, suggesting altered transmission dynamics. We found that a model forced with the period obtained by local power wavelet decomposition best fit and forecast observations. In addition, the MME performed the best across the entire study period. Finally, our study included US-level data until 2022, allowing study of a possible IMD rebound after relaxation of non-pharmaceutical interventions imposed in response to the COVID-19 pandemic; however, no evidence of a rebound was found. Our findings demonstrate the ability of process-based models to retrospectively forecast IMD and provide a first analysis of the seasonality of IMD before and after the complete vaccination regimen.