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Background: The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated., Methods: Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006-2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution., Results: Among 188 N. meningitidis culture-positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points., Conclusion: We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV., Methods: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis., Results: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9-42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6-35.1) and the anal rate was 11.0% (95% CI 5.1-19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up., Conclusion: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Neisseria meningitidis can cause sporadic cases and outbreaks of invasive disease, including meningitis and sepsis. The meningococcal serogroup C (MenC) is the second most common serogroup in Italy after MenB. In this study we have estimated the reproductive numbers and the demographic reconstruction on the genomes of invasive N. meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11) strains isolated in Italy in 2012 - 2017, a period that includes the outbreak in Tuscany., Methods: The genomes of N. meningitidis were sequenced using the Illumina MiSeq platform, through the whole genome sequencing (WGS) method and were analyzed by the core genome MLST (cgMLST) approach, using the BIGSdb Genome Comparator tool implemented on the PubMLST website. A Bayesian method was applied to study population dynamics across the entire N. meningitidis dataset. The basic reproduction number R 0, which indicates the average number of secondary cases generated by a single primary case, was calculated using a Bayesian method, on the dataset and on the two subsets. The effective reproduction number R(t), defined as the average number of secondary cases per infectious case in a population, made up of susceptible and non-susceptible hosts was studied on the Tuscany dataset, with a Bayesian method., Results: An increase in the effective number of the N. meningitidis infections was observed between 2013 and 2016. The estimated R 0 parameter was 1.31 (95% HPD: 1.03 - 1.64), 1.22 (95% HPD: 0.90 - 1.64) and 1.4 (95% HPD: 0.91 - 1.9) for the entire dataset, first and second subset, respectively. The BDSKY estimated an initial R(t) of about 2.0 (95% HPD: 0.04 - 5.0), which showed a growing trend at the end of 2014, reaching an average value of 3.22 in 2015, and then declining below 1 from the year 2016., Conclusion: Monitoring the effective reproduction number can help to inform future vaccination strategies. The increase in the reproductive number for the Tuscany dataset, was consistent with the amplification event that led to the Tuscany outbreak. Subsequently, the intervention that led to the decline of the cases was followed, suggesting a high effectiveness of the vaccination campaign., Competing Interests: Declaration of Competing Interest The authors do not have any disclosures to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Pharyngeal carriage is the reservoir for Neisseria meningitidis in the population and the first step in disease transmission. Especially in young infants and adolescents, N. meningitidis can cause serious invasive infection with high fatality rates and high rates of long-term sequelae among survivors. The aim of this study was to determine N. meningitidis colonization rates in asymptomatic health care professionals at a tertiary university pediatric hospital and to identify risk factors for carriage. This cross-sectional meningococcal carriage survey was conducted between April and October 2018 at the Medical University of Vienna. Individuals working as nurses, pediatricians, or medical students were enrolled. Oropharyngeal swabs were directly plated onto selective agar plates and conventional culture was used for bacterial identification. Meningococcal isolates were further characterized using whole-genome sequencing. A total of 437 oropharyngeal specimens were collected. Overall, meningococcal carriage prevalence was 1.14% (5/437), with 0.7% (3/437) for capsular genotype B, and 0.5% (2/437) for capsular genotype W. Mean age of carriers was significantly lower than of non-carriers (24.2 vs. 35.8; p = 0.004). The highest carriage rate of 4.4% (4/91) was found in the age group 18-25. Carriage was negatively associated with age and timespan working in pediatrics. This is the first study evaluating the prevalence of Neisseria meningitidis carriage in health care professionals working in Pediatrics and Adolescent Medicine. Carriage was in general lower than expected for all age groups, implicating a low risk of meningococcal transmission via this population.

Neisseria meningitidis is an obligate human commensal bacterium that frequently colonises the upper respiratory tract. Person-to-person transmission occurs via direct contact or through dispersion of respiratory droplets from a carrier of the bacteria, and can lead to invasive meningococcal disease. Rare sporadic cases of meningococcal urogenital and anorectal infections, including urethritis, proctitis, and cervicitis, have been reported, typically following orogenital contact with an oropharyngeal meningococcal carrier. The resulting infections were clinically indistinguishable from infections caused by Neisseria gonorrhoeae. Over the past two decades, there have also been multiple outbreaks across North America and Europe of invasive meningococcal disease among men who have sex with men (MSM). The responsible meningococci belong to a highly virulent and predominantly serogroup C lineage, including strains that are able to express nitrite reductase and grow in anaerobic environments, such as the urogenital and anorectal tracts. More recently, a distinct clade within this lineage has expanded to cause urethritis predominantly among men who have sex with women. Evolutionary events giving rise to this clade included the loss of the ability to express a capsule, and acquisition of several gonococcal alleles, including one allele encoding a highly efficient gonococcal nitrite reductase. Members of the clade continue to acquire gonococcal alleles, including one allele associated with decreased antibiotic susceptibility. This evolution has implications for the clinical and public health management of those who are infected and their close contacts, in terms of both antibiotic treatment, and prevention through vaccination., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Serogroup B meningococci (MnB) are now the largest cause of invasive meningococcal disease (IMD) in Canada. We assessed the clinical and economic impact of 3 adolescent MenB-FHbp immunization strategies., Methods: A population-based dynamic transmission model was developed to simulate the transmission of MnB among the entire Canadian population over a 30-year time horizon. Age group-based IMD incidence, bacterial carriage and transmission, disease outcomes, costs, and impact on quality of life were obtained from Canadian surveillance data and published literature. The vaccine was assumed to provide 85% protection against IMD and 26.6% against carriage acquisition. The model estimated the impact of routine vaccination with MenB-FHbp in 3 strategies: (1) age 14, along with existing school-based programs, with 75% uptake; (2) age 17 with 75% uptake, assuming school vaccination; and (3) age 17 with 30% uptake, assuming vaccination outside of school. Costs were calculated from the Canadian societal perspective., Results: With no vaccination, an estimated 3974 MnB cases would be expected over 30 years. Vaccination with strategies 1-3 were estimated to avert 688, 1033, and 575 cases, respectively. These outcomes were associated with incremental costs per quality-adjusted life-year of $976,000, $685,000, and $490,000., Conclusions: Our model indicated that if the vaccine reduces risk of carriage acquisition, vaccination of older adolescents, even at lower uptake, could have a significant public health impact. Due to low disease incidence, MnB vaccination is unlikely to meet widely accepted cost-effectiveness thresholds, but evaluations of new programs should consider the overall benefits of the vaccination.

In 2015, a suspected cluster of two invasive meningococcal disease (IMD) cases of serogroup W Neisseria meningitidis (MenW) occurred in elderly care home residents in England over 7 months; case investigations followed United Kingdom guidance. An incident control team reviewed epidemiological information. Phenotyping of case specimens informed public health action, including vaccination and throat swabs to assess carriage. Whole genome sequencing (WGS) was conducted on case and carrier isolates. Conventional phenotyping did not exclude a microbiological link between cases (case 1 W:2a:P1.5,2 and case 2 W:2a:NT). After the second case, 33/40 residents and 13/32 staff were vaccinated and 19/40 residents and 13/32 staff submitted throat swabs. Two MenW carriers and two MenC carriers were detected. WGS showed that MenW case and carrier isolates were closely related and possibly constituted a locally circulating strain. Meningococcal carriage, transmission dynamics and influence of care settings on IMD in older adults are poorly understood. WGS analyses performed following public health action helped to confirm the close relatedness of the case and circulating isolates despite phenotypic differences and supported actions taken. WGS was not sufficiently timely to guide public health practice.

Beginning in 1974, the date on which the Expanded Program on Immunization was established in the Americas, the number of deaths and disabilities due to certain infectious diseases decreased considerably thanks to universally applied vaccines. A program that initially included four vaccines that protected against six diseases (tuberculosis, diphtheria, pertussis, tetanus, polio and measles) was consolidated, over the years, by incorporating new vaccines and significantly raising coverage rates. The Sociedad Argentina de Pediatría (Argentine Society of Pediatrics), as a leader of opinion, played a leading role in the incorporation of new vaccines, currently reaching one of the most complete vaccination calendars in the world, which improves the levels of inequality and inequity in public health. Taking into account the significant role of the pediatrician in decision-making, the National Committee of Infectious Diseases, together with the Subsidiary Committees, prepared a document on updates and recommendations for 2018 on Polio, Rotavirus, Pneumococcus, Meningococcus, Human Papillomavirus, Chickenpox, Flu, Dengue vaccines and Whooping Cough., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Objectives: The aim was to investigate an outbreak of invasive meningococcal disease (IMD) in Southern Sardinia., Methods: Epidemiological and microbiological investigations were performed. The latter included antimicrobial susceptibility testing and whole-genome sequencing (WGS)., Results: Seven individuals with severe IMD were found to be infected with serogroup B (MenB) Neisseria meningitidis in the first quarter of 2018. Five of the seven cases (five males; mean age 19 years; range 18-21 years; CFR 40%) were due to a unique strain B:P1.5-1,10-8:F3-6:ST-11(cc11), probably switched from the hypervirulent C-cc11, as confirmed by WGS. All five patients had attended the same nightclub in the 2 weeks prior to symptom onset. Public health measures, including chemoprophylaxis of contacts and active immunization against MenB, were implemented., Conclusions: We observed five IMD cases due to the same switched MenB strain. The hypervirulent B:P1.5-1,10-8:F3-6:ST-11(cc11) strain, probably switched from C-cc11, is of concern due to the observed high virulence and case fatality rates. All the patients shared the same place of probable exposure. The molecular characterization of the invasive strain allowed the outbreak to be confirmed, which was then controlled through timely public health action., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is characterized by high mortality and morbidity. While IMD incidence peaks in both infants and adolescents/young adults, carriage rates are often highest in the latter age groups, increasing IMD risk and the likelihood of transmission. Effective vaccines are available for 5 of 6 disease-causing serogroups. Because adolescents/young adults represent a significant proportion of cases, often have the highest carriage rate, and have characteristically low vaccination adherence, efforts should be focused on educating this population regarding long-term consequences of infection and the importance of meningococcal vaccination in prevention. This review describes the role of adolescents/young adults in meningococcal transmission and the clinical consequences and characteristics of IMD in this population. With a focus on countries with advanced economies that have specific meningococcal vaccination recommendations, the epidemiology of meningococcal disease and vaccination recommendations in adolescents/young adults will also be discussed.

Neisseria meningitidis sequence type 11 is an emerging cause of urethritis. We demonstrate by using whole-genome sequencing orogenital transmission of a N. meningitidis sequence type 11 isolate causing urethritis in a monogamous couple of men who have sex with men. These results suggest dissemination of this clonal complex among low-risk patients.

Background: Mass gatherings (MGs) such as the Hajj and Umrah pilgrimages are known to amplify the risk of invasive meningococcal disease (IMD) due to enhanced transmission of the organism between attendees. The burden of IMD at MGs other than Hajj and Umrah has not previously been quantified through a systematic review., Methods: A systematic search for relevant articles in PubMed and Embase was conducted using MeSH terms; this was buttressed by hand searching. Following data abstraction, a narrative synthesis was conducted to quantify the burden of IMD at MGs and identify potential risk factors and mitigation measures., Results: Thirteen studies reporting occurrence of IMD at MGs or similar crowded settings were identified. Eight studies reported cases or outbreaks in MGs of ≥1000 people; five others reported IMD in other crowded settings; all occurred between 1991 and 2015. All age groups were involved in the identified studies; however the majority of cases (∼80%) were young people aged 15-24 years. The number of affected people ranged from one to 321 cases and the overall crude estimate of incidence was calculated as 66 per 100,000 individuals. Serogroups A, C, B and W were identified, with serogroups A and C being most common. Of 450 cases of IMD reported in non-Hajj/Umrah MGs, 67 (14.9%) had fatal outcomes., Conclusion: IMD outbreaks at non-Hajj/Umrah MGs are generally much smaller than Hajj-related outbreaks and affect mainly young people. Health education and vaccination should be considered for attendees of high risk non-Hajj/Umrah MGs, especially those involving adolescents and young adults., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The Hajj and Umrah mass gatherings represent many of the risk factors for meningococcal disease and have historically been associated with both local and international outbreaks of the disease. The implementation of strict preventative measures including mandatory meningococcal vaccination with the quadrivalent (A,C,Y,W) vaccine has prevented pilgrimage-associated meningococcal outbreaks and significantly reduced the incidence of the disease at these events. However, meningococcal disease remains an important public health threat at the Hajj and Umrah due in part to the evolving nature of the disease, characterized with diverse and varying geographic trends, fluctuations in incidence and shifts in serogroups and genotypes. In addition, the current Hajj and Umrah meningococcal disease preventative measure do not protect against all invasive serogroups and do not necessarily affect carriage and transmission as the polysaccharide vaccine is still widely used. As a consequence, these events are still susceptible to outbreaks of the disease including those due to serogroups not included in the required vaccines such as serogroups B and X. In this context, despite the global decline in incidence of meningococcal disease, including that cause by serogroup B, the increased predominance of serogroup B disease in many countries, including countries with large Muslim populations, and the emergence of serogroup X in the African meningitis belt, are particularly concerning. Continued and strict surveillance of meningococcal diseases nationally and globally, especially in Muslim countries, is essential in detecting, understanding, and predicting the changes in the epidemiology of the disease and informing appropriate prevention and control strategies during these events. The current meningococcal disease preventative measures for Hajj and Umrah should continue to be strictly implemented, reviewed regularly and updated in accordance with changes in the epidemiology of meningococcal disease and availability of new preventative tools including new vaccines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Colonization of the human nasopharyngeal tract by the bacterium Neisseria meningitidis is usually asymptomatic, but life-threatening meningococcal disease with a clinical presentation of meningitis, septicemia, or more rarely, gastrointestinal symptoms, can develop. Invasive meningococcal disease (IMD) can be fatal within 24 hours, but IMD is vaccine-preventable. Vaccines used to protect against IMD caused by 5 of the 6 most common serogroups (A, B, C, W, and Y) may also influence carriage prevalence in vaccinated individuals. Lower carriage among vaccinated people may reduce transmission to nonvaccinated individuals to provide herd protection against IMD. This article reviews observational and clinical studies examining effects of vaccination on N. meningitidis carriage prevalence in the context of mass vaccination campaigns and routine immunization programs. Challenges associated with carriage studies are presented alongside considerations for design of future studies to assess the impact of vaccination on carriage.

The aims of the study were to estimate the carrier state of Neisseria meningitidis in Swedish teenagers and its association with an outbreak at the World Scout Jamboree in 2015 as well as to compare sensitivity of throat versus nasopharyngeal swab for optimal detection of carriage. In total, 1 705 samples (cultures n = 32, throat swabs n = 715, nasopharyngeal swabs n = 958) from 1 020 Jamboree participants were collected and sent to the National Reference Laboratory for Neisseria meningitidis for culture and molecular analysis. The overall positivity for N. meningitidis was 8% (83/1 020), whereas 2% (n = 22) belonged to a known sero/genogroup while the majority (n = 61) were non-groupable. Throat sample is clearly the sampling method of choice, in 56 individuals where both throat and nasopharynx samples were taken, N. meningitidis was detected in both throat and nasopharynx in eight individuals, in 46 individuals N. meningitidis was only detected in the throat and in two individuals only in the nasopharynx. Carriage studies are important to provide knowledge of the current epidemiology and association between carrier isolates and disease-causing isolates in a given population. Therefore, planning for a carriage study in Sweden is in progress., (© 2018 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Medical Microbiology and Pathology.)

Objectives: Carriers of Neisseria meningitidis are a key source of transmission. In the African meningitis belt, where risk of meningococcal disease is highest, a greater understanding of meningococcal carriage dynamics is needed., Methods: We randomly selected an age-stratified sample of 400 residents from 116 households in Bamako, Mali, and collected pharyngeal swabs in May 2010. A month later, we enrolled all 202 residents of 20 of these households (6 with known carriers) and collected swabs monthly for 6 months prior to MenAfriVac vaccine introduction and returned 10 months later to collect swabs monthly for 3 months. We used standard bacteriological methods to identify N. meningitidis carriers and fit hidden Markov models to assess acquisition and clearance overall and by sex and age., Results: During the cross-sectional study 5.0% of individuals (20/400) were carriers. During the longitudinal study, 73 carriage events were identified from 1422 swabs analyzed, and 16.3% of individuals (33/202) were identified as carriers at least once. The majority of isolates were non-groupable; no serogroup A carriers were identified., Conclusions: Our results suggest that the duration of carriage with any N. meningitidis averages 2.9 months and that males and children acquire and lose carriage more frequently in an urban setting in Mali. Our study informed the design of a larger study implemented in seven countries of the African meningitis belt., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neisseria meningitidis is a gram-negative bacterium that lives as a commensal in the human nasopharynx. Meningococci are generally non-invasive, but can invade the nasopharyngeal epithelia and enter the bloodstream causing life-threatening illnesses. It is generally thought that meningococci do not survive for long outside the host, and that transmission requires relatively close contact between hosts. There are some reports, however, that meningococci can survive drying on surfaces, including glass, plastic and cloth. Our examination of N. meningitidis strains dried on glass showed differences in survival of isolates belonging to serogroups B, C and W135, including persistence of Cuban, New Zealand, and Norwegian epidemic strains up to 8 days, depending on temperature and humidity. Survival of a New Zealand epidemic strain isolate NZ98/254 under ambient conditions in the laboratory was greatest in winter suggesting that environmental factors impacted survival. For most isolates, including NZ98/254, survival under controlled conditions at 30 °C was greater at 22% than 30% relative humidity. There were also some differences in survival between carriage and invasive strains. The results suggest that N. meningitidis could be transmitted through contact with surfaces outside the host, potentially including contact through shared drinking vessels.

Background and aims of the work: Invasive Meningococcal Disease (IMD) represents a global health threat, and occupational settings have the potential to contribute to its spreading. Therefore, here we present the available evidences on the epidemiology of IMD on the workplaces., Methods: The following key words were used to explore PubMed: Neisseria meningitidis, meningococcus, meningococcal, invasive meningococcal disease, epidemiology, outbreaks, profession(al), occupation(al)., Results: We identified a total of 12 IMD cases among healthcare workers (HCW), 44 involving biological laboratory workers (BLW), 8 among school personnel, and eventually 27 from other settings, including 3 large industrial working populations. Eventual prognosis of BLW, particularly the case/fatality ratio, was dismal. As clustered in time and space, data about school cases as well as industrial cases seem to reflect community rather than occupational outbreaks. In general, we identified a common pattern for HCW and BLW, i.e. the exposure to droplets or aerosol containing N meningitidis in absence of appropriate personal protective equipment (PPE) and/or microbiological safety devices (MSD) (e.g. cabinets). Post-exposure chemoprophylaxis (PEC) was rarely reported by HCW (16.7%) workers, and never by BLW. Data regarding vaccination status were available only for a case, who had failed requested boosters., Conclusions: The risk for occupational transmission of IMD appears relatively low, possibly as a consequence of significant reporting bias, with the exception of HCW and BLW. Improved preventive measures should be implemented in these occupational groups, in order to improve the strict use of PPE and MSD, and the appropriate implementation of PEC.

The article presents the prevalence of Neisseria meningitidis carriage with the identification of sero- and genogroups in professional soldiers serving in the Polish Armed Forces. A total of 1246 soldiers from the 10th Armored Cavalry Brigade in Świętoszów, Poland were examined in the period January-February 2016. Microbiological tests were performed using standard methods (culture, incubation, microscopy, biochemical, and automated identification with VITEK cards). Neisseria meningitidis isolates from carriers were subjected to a slide agglutination test for the identification of serogroups, next bacterial DNA was isolated and genogroups were identified based on the results of PCR. Of the 1246 soldiers tested, 65 were found to be carriers of N. meningitidis. Serogroups of 36 isolates and genogroups of 56 meningococcal isolates were determined. The genogrouping identified the isolates as belonging to group B (n = 34; 52.3 %), E29 (n = 8; 12.3 %), C (n = 6; 9.2 %), Y (n = 6; 9.2 %), and W (n = 2; 3.1 %). The primers which were used did not make it possible to determine the genogroup of nine isolates. In conclusion, the overall carrier rate of N. meningitidis amounted to 5.2 %, with the serogroup B being predominant, which is similar to that reported in the general population in Poland and Central Europe.

A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates., (Copyright © 2016 Mulhall et al.)

Purpose: The aim of the study was to estimate the meningococcal carriage rate and to identify the genotypic characteristics of the strains isolated from healthy military recruits and university students in order to provide data that might increase our understanding on the epidemiology of meningococcus and obtain information which helps to evaluate the potential effects on control programs such as vaccination., Methods: A total of 1420 oropharyngeal single swab samples were collected from military recruits and university students on voluntary basis, aged 18-26 years. New York City Medium was used for culture and the suspected N. meningitidis colonies were identified by Gram stain, oxidase and rapid carbohydrate utilization tests. Further characterisation was carried out by molecular methods (multiplex PCR, MLST, WGS)., Results: The overall carriage rate was of 12.7%; 15% and 10.4% for recruits and university students respectively. MenB (39.4%) was the most prevalent followed by MenY (12.8%) and MenW (4.4%). Among the initial 76 Non Groupable (NG) isolates, Whole Genome Sequence Analysis (WGS) revealed that 8.3% belonged to MenE, 3.3% to MenX and 1.1% to MenZ, while, 53 strains (29.4%) were finally identified as capsule null. Genetic diversity was found among the MenB isolates, with 41/44 cc and 35 cc predominating., Conclusion: Meningococcal carriage rate in both groups was lower compared to our previous studies (25% and 18% respectively) with predominance of MenB isolates. These findings, help to further our understanding on the epidemiology of meningococcal disease in Greece. Although the prevalence of carriage seems to have declined compared to our earlier studies, the predominant MenB clonal complexes (including 41/44cc and 35cc) are associated with invasive meningococcal disease., Competing Interests: The pricipal investigator of this study (GT) has received funding from GSK. This does not alter the adherence to all PLOS ONE policies on sharing data and materials. The rest of co-authors declare that no competing interests exist.

The Kingdom of Saudi Arabia (KSA) has a long history of instituting preventative measures against meningococcal disease (MD). KSA is at risk of outbreaks of MD due to its geographic location, demography, and especially because it hosts the annual Hajj and Umrah mass gatherings. Preventative measures for Hajj and Umrah include vaccination, targeted chemoprophylaxis, health awareness and educational campaigns, as well as an active disease surveillance and response system. Preventative measures have been introduced and updated in accordance with changes in the epidemiology of MD and available preventative tools. The mandatory meningococcal vaccination policy for pilgrims has possibly been the major factor in preventing outbreaks during the pilgrimages. The policy of chemoprophylaxis for all pilgrims arriving from the African meningitis belt has also probably been important in reducing the carriage and transmission of Neisseria meningitidis in KSA and beyond. The preventative measures for Hajj and Umrah are likely to continue to focus on vaccination, but to favour the conjugate vaccine for its extra benefits over the polysaccharide vaccines. Additionally, the surveillance system will continue to be strengthened to ensure early detection and response to cases and outbreaks; ongoing disease awareness campaigns for pilgrims will continue, as will chemoprophylaxis for target groups. Local and worldwide surveillance of the disease and drug-resistant N. meningitidis are crucial in informing future recommendations for vaccination, chemoprophylaxis, and treatment. Preventative measures should be reviewed regularly and updated accordingly, and compliance with these measures should be monitored and enhanced to prevent MD during Hajj and Umrah, as well as local and international outbreaks., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Meningococcal disease is a serious public health threat, especially during mass gatherings such as Hajj and Umrah which provide optimal conditions for disease transmission. The disease is caused by Neisseria meningitidis and transmitted mainly via asymptomatic carriers. A review of the literature on asymptomatic N. meningitidis carriage among Hajj and Umrah pilgrims and their household contacts was performed. Carriage studies reported carriage rates to be higher in Hajj pilgrims compared to Umrah pilgrims and that these events promote acquisition of carriage among pilgrims. With some outliers, most studies found carriage rates among pilgrims to be comparable to those in populations under non-epidemic settings. However, these results should be interpreted with caution, taking into account the limitations within the studies identified. A wide variety of N. meningitidis serogroups appear to be circulating among Hajj and Umrah pilgrims, with serogroups W135 and B being most prominent. Current Hajj and Umrah meningococcal disease preventative measures do not necessarily prevent carriage and transmission, which may result in local and international outbreaks among susceptible populations. Monitoring carriage states of visitors and local inhabitants in the Kingdom of Saudi Arabia, as well as the implementation of preventive measures that impact carriage, are warranted to reduce the risk of Hajj and Umrah-related meningococcal disease outbreaks., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 49-year-old diabetic man presented with a 2-day history of a painful right eye associated with a purulent discharge. Prior to becoming symptomatic, he reported that someone spat at him, resulting in direct contact between the saliva and his affected eye. Gram stain revealed numerous leucocytes with Gram-negative diplococci, and culture yielded Neisseria meningitidis (serogroup C). There was no evidence of any systemic infection, and blood cultures were negative for any growth. He was treated for primary meningococcal conjunctivitis (PMC) with intensive topical antibiotic eyedrops as well as systemic antibiotics. One week after commencing treatment he remained systemically well and his symptoms had fully resolved.

In December 2013 Bexsero® became available in Germany for vaccination against serogroup B meningococci (MenB). In August 2015 the German Standing Committee on Vaccination (STIKO) endorsed a recommendation for use of this vaccine in persons at increased risk of invasive meningococcal disease (IMD). This background paper summarizes the evidence underlying the recommendation. Bexsero® is based on surface protein antigens expressed by about 80% of circulating serogroup B meningococci in Germany. The paper reviews available data on immunogenicity and safety of Bexsero® in healthy children and adolescents; data in persons with underlying illness and on the effectiveness in preventing clinical outcomes are thus far unavailable.STIKO recommends MenB vaccination for the following persons based on an individual risk assessment: (1) Persons with congenital or acquired immune deficiency or suppression. Among these, persons with terminal complement defects and properdin deficiency, including those under eculizumab therapy, are at highest risk with reported invasive meningococcal disease (IMD) incidences up 10,000-fold higher than in the general population. Persons with asplenia were estimated to have a ~ 20-30-fold increased risk of IMD, while the risk in individuals with other immune defects such as HIV infection or hypogammaglobulinaemia was estimated at no more than 5-10-fold higher than the background risk. (2) Laboratory staff with a risk of exposure to N. meningitidis aerosols, for whom an up to 271-fold increased risk for IMD has been reported. (3) Unvaccinated household (-like) contacts of a MenB IMD index case, who have a roughly 100-200-fold increased IMD risk in the year after the contact despite chemoprophylaxis. Because the risk is highest in the first 3 months and full protective immunity requires more than one dose (particularly in infants and toddlers), MenB vaccine should be administered as soon as possible following identification of the serogroup of the index case.

N. meningitidis is a major cause of meningitis and septicemia and a major public health problem in many countries. The disease, that can be fulminant, has a high mortality and may cause serious sequelae, even in cases of apparently optimal medical treatment. Chemoprophylaxis may prevent secondary cases among those in close contact with the ill, but, since secondary cases represent only 1%-2% of all meningococcal disease, chemoprophylaxis has a small impact when fighting most of endemic and epidemic forms. Given that al least 5% -15% of children and young adults are carriers, the fight against meningococcal disease based on chemotherapeutic elimination of nasopharyngeal colonization is virtually impossible. Therefore, immunization is the only rational way to combat this disease., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

The exclusive reservoir of the genus Neisseria is the human. Of the broad range of species that comprise the Neisseria, only two are frequently pathogenic, and only one of those is a resident of the nasopharynx. Although Neisseria meningitidis can cause severe disease if it invades the bloodstream, the vast majority of interactions between humans and Neisseria are benign, with the bacteria inhabiting its mucosal niche as a non-invasive commensal. Understandably, with the exception of Neisseria gonorrhoeae, which preferentially colonises the urogenital tract, the neisseriae are extremely well adapted to survival in the human nasopharynx, their sole biological niche. The purpose of this review is to provide an overview of the molecular mechanisms evolved by Neisseria to facilitate colonisation and survival within the nasopharynx, focussing on N. meningitidis. The organism has adapted to survive in aerosolised transmission and to attach to mucosal surfaces. It then has to replicate in a nutrition-poor environment and resist immune and competitive pressure within a polymicrobial complex. Temperature and relative gas concentrations (nitric oxide and oxygen) are likely to be potent initial signals of arrival within the nasopharyngeal environment, and this review will focus on how N. meningitidis responds to these to increase the likelihood of its survival., (© 2015 Elsevier Ltd. All rights reserved.)

Background/aim: The annual Hajj pilgrimage to Mecca, which attracts more than 3 million Muslim pilgrims from around the world, has played a role in the global spread of meningococcal infection. We aimed to compare pharyngeal carriage of Neisseria meningitidis in Hajj pilgrims before departure and after returning to Iran, Zahedan., Materials and Methods: This prospective and cross-sectional study was conducted among Hajj pilgrims in Zahedan (southeast Iran) in 2012. We studied all pilgrims who agreed to participate in this study and who met the inclusion criteria. Sampling was done by swabbing the posterior pharyngeal wall through the mouth with direct plating or keeping transport time to below 5 h. Specific culture, oxidase test, and carbohydrates tests were done on the positive samples., Results: Among 422 pilgrims (42.2% male, 57.8% female; with age range 21-95 years), 6 (1.4%) were positive for N. meningitidis after the Hajj pilgrimage. Nobody was positive before departure. During the Hajj 58.5% of the participants received antibiotics., Conclusion: According to the results of our study, the prevalence of pharyngeal carriage of N. meningitidis in pilgrims after returning to Zahedan was low (1.4%). The quadrivalent meningococcal vaccine and antibiotic therapy were effective in reducing the number of carriers among pilgrims after travel.

Objective: Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers., Methods: We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U) to swabbing the posterior pharynx behind the uvula plus one tonsil (T). Swabs were cultured immediately and analyzed using molecular methods., Results: One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6%) based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7%) versus 4.9% (95% CI: 3.6-6.4%) respectively (p=0.6)). The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73), indicating good agreement., Conclusions: These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.

Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons.

This paper reviews the epidemiological data describing meningococcal disease in the Middle East and North Africa (MENA). While meningococcal disease remains an important cause of endemic and epidemic disease in many MENA countries, existing published epidemiological data appear limited, fragmented, and collected via disparate methodologies. Children aged 5 years and younger are predominantly affected, though outbreaks of the disease often affect older age groups. Whilst serogroup A remains a main cause of meningococcal disease in the region, cases of serogroup B, W-135, and Y have been increasingly reported over the last two decades in some countries. The Hajj pilgrimage is a key factor influencing outbreaks and transmission, and the use of vaccines has minimized the effects on the home countries of the pilgrims and has decreased global dissemination of disease. Wider use of available polyvalent meningococcal conjugate vaccines may provide broader protection against the range of serogroups causing disease or posing a threat in the region. In addition, strengthening regional surveillance systems and regularly publishing reports with reliable estimates of disease incidence, carriage, disease-related mortality, and sequelae may facilitate the development of appropriate interventions and public health strategies regarding meningococcal disease within the region., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In August 2010, the New York City Department of Health and Mental Hygiene (DOHMH) conducted an investigation to identify and provide antibiotic prophylaxis to close contacts of a patient who had died of invasive meningococcal disease. Traditional contact tracing, which relies on interviews with the patient's close associates, identified 3 persons meeting prophylaxis criteria. In addition, DOHMH learned of an Internet site used by the patient to arrange anonymous sexual encounters. By working with the Internet site administrator through a liaison, DOHMH sent notification to 15 additional persons potentially at risk for meningococcal disease; of those, at least 1 met prophylaxis criteria. The Internet has been used previously for partner notification by sexually transmitted disease control programs. This case report illustrates how the Internet can aid contact investigations for other communicable diseases, especially when identifying potential contacts is urgent, patients have died, or contacts are unknown to the patient's associates.

A novel point process model continuous in space-time is proposed for quantifying the transmission dynamics of the two most common meningococcal antigenic sequence types observed in Germany 2002-2008. Modeling is based on the conditional intensity function (CIF), which is described by a superposition of additive and multiplicative components. As an epidemiological interesting finding, spread behavior was shown to depend on type in addition to age: basic reproduction numbers were 0.25 (95% CI 0.19-0.34) and 0.11 (95% CI 0.07-0.17) for types B:P1.7-2,4:F1-5 and C:P1.5,2:F3-3, respectively. Altogether, the proposed methodology represents a comprehensive and universal regression framework for the modeling, simulation, and inference of self-exciting spatiotemporal point processes based on the CIF. Usability of the modeling in biometric practice is promoted by an implementation in the R package surveillance., (© 2011, The International Biometric Society.)

Pregnant health care workers (HCW) may be exposed to pathogens during routine patient care duties. Although they do not seem to be at higher risk for infection compared with nonpregnant HCW, certain infections can be associated with increased maternal morbidity, mortality, and adverse perinatal outcomes. Primary prevention through vaccination is crucial. Medical providers must know which vaccines are safe during pregnancy and which should be postponed until after delivery. Pregnancy should not be a contraindication for certain postexposure prophylaxis regimens after an occupational exposure. Pregnant HCW need to be educated about specific occupational risks and the recommended infection control precautions.

A cluster of four confirmed cases of meningococcal disease was seen in the same nuclear family across a 15-week period. The cases were three siblings and a parent and all recovered well. The first case was confirmed by meningococcal PCR only but the subsequent three cases were due to indistinguishable strains of serogroup B (B:NT:P1.19-1,15-11). Contact tracing was initially undertaken and reviewed in detail after each subsequent case. Antibiotic prophylaxis was administered to close family contacts on three separate occasions, including switching of antibiotic agents, with good compliance. Subsequent investigation of the family has not revealed any obvious immunological problem and no further significant infections have been recognised. A cluster of meningococcal disease of this nature and timescale is highly unusual. Details of the cluster, investigation and implications for health protection practice are discussed.

Serogroup B meningococcal disease is the last main cause of bacterial meningitis and septicaemia in the UK. There is currently no vaccine against this serogroup. This article outlines the nature of meningococcal disease and highlights recent guidance from the National Institute for Health and Clinical Excellence on recognising and managing the disease in primary and secondary care. An update on progress towards a preventive vaccine is also discussed.

A scientist in our laboratory was accidentally infected while working with Z5463, a Neisseria meningitidis serogroup A strain. She developed severe symptoms (fever, meningism, purpuric lesions) that fortunately evolved with antibiotic treatment to complete recovery. Pulse-field gel electrophoresis confirmed that the isolate obtained from the blood culture (Z5463BC) was identical to Z5463, more precisely to a fourth subculture of this strain used the week before the contamination (Z5463PI). In order to get some insights into genomic modifications that can occur in vivo, we sequenced these three isolates. All the strains contained a mutated mutS allele and therefore displayed an hypermutator phenotype, consistent with the high number of mutations (SNP, Single Nucleotide Polymorphism) detected in the three strains. By comparing the number of SNP in all three isolates and knowing the number of passages between Z5463 and Z5463PI, we concluded that around 25 bacterial divisions occurred in the human body. As expected, the in vivo passage is responsible for several modifications of phase variable genes. This genomic study has been completed by transcriptomic and phenotypic studies, showing that the blood strain used a different haemoglobin-linked iron receptor (HpuA/B) than the parental strains (HmbR). Different pilin variants were found after the in vivo passage, which expressed different properties of adhesion. Furthermore the deletion of one gene involved in LOS biosynthesis (lgtB) results in Z5463BC expressing a different LOS than the L9 immunotype of Z2491. The in vivo passage, despite the small numbers of divisions, permits the selection of numerous genomic modifications that may account for the high capacity of the strain to disseminate.