Effectiveness of quadrivalent meningococcal conjugate vaccine against meningococcal carriage and genotype character changes: A secondary analysis of prospective cohort study in Korean military trainees.

OBJECTIVE: We evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. METHODS: Oropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). RESULTS: Of 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P = 0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95% CI: 36.3-88.2), and serogroup C was particularly reduced (VEC = 83.0%, 95% CI: 50.6-94.1), whereas non-groupable isolates increased significantly after vaccination (VENG = -76.1%, 95% CI: -176.2 to -13.1). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. CONCLUSIONS: MenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.

Evaluation of antibody responses in healthcare workers before & after meningococcal vaccine and determination of meningococcal carriage rates.

The rates of nasopharyngeal meningococcal carriage in healthcare workers are unknown. Meningococcal vaccine is recommended for risk groups but healthcare workers are not included in risk groups for many countries. Herein, we aimed to investigate the nasopharyngeal meningococcal carriage rates, basal and after one dose of Men-ACWY-DT vaccine response on the 30th day by evaluating meningococcus IgG antibody levels and decolonization at month six after vaccination among the detected carriers. Nasopharyngeal swab samples were taken before vaccination to evaluate meningococcal carriage in healthcare workers. All participants received a single dose of Men-ACWY-DT vaccine. Serum samples were collected immediately before vaccination and again on day 30 post-vaccination. Antibodies in the stored sera were analyzed using the ELISA method. Participants who were determined to carry meningococci at the initial visit underwent another round of nasopharyngeal swab tests six months post-vaccination to check for decolonization. Between November 2020 and May 2021, we evaluated samples from 100 physicians [52 % females, 28.28 ± 4.45 (min: 24, max: 49)]. The majority of the physicians worked in the emergency department (45 %), followed by the infectious diseases clinic (14 %). Fifty-eight physicians had a history of at least one contact with a meningococcus-infected patient, and 53 (91.4 %) had used prophylactic antibiotics at least once due to this exposure. None of the study group nasopharyngeal swab cultures were positive for Neisseria meningitidis. Before the Men-ACWY-DT vaccine, anti-meningococcus IgG positivity was detected in the serum samples of only 3 (3 %) participants. By day 30 after vaccination, 48 % of participants showed positive for antibodies. As we didn't detect nasopharyngeal carriage in any participants, we didn't evaluate decolonization among carriers six months post-vaccination. Notably, detection of antibodies was evident in about half of the participants on day 30 after receiving a single dose of the Men-ACWY-DT vaccine.

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.

The genomic epidemiology of Neisseria meningitidis carriage from a randomised controlled trial of 4CMenB vaccination in an asymptomatic adolescent population.

Background: Oropharyngeal carriage of Neisseria meningitidis is frequent during adolescence, representing a major source of invasive meningococcal disease. This study examined the impact of a serogroup B vaccination (Bexsero, GSK 4CMenB) programme on adolescent N. meningitidis carriage using genomic data. Methods: A total 34,489 oropharyngeal samples were collected as part of a state-wide cluster randomised-controlled trial in South Australia during 2017 and 2018 (NCT03089086). Samples were screened for the presence of N. meningitidis DNA by porA PCR prior to culture. Whole genome sequencing was performed on all 1772 N. meningitidis culture isolates and their genomes were analysed. Findings: Unencapsulated meningococci were predominant at baseline (36.3% of isolates), followed by MenB (31.0%), and MenY (20.5%). Most MenB were ST-6058 from hyperinvasive cc41/44, or ST-32 and ST-2870 from cc32. For MenY, ST-23 and ST-1655 from cc23 were prevalent. Meningococcal carriage was mostly unchanged due to the vaccination programme; however, a significant reduction in ST-53 capsule-null meningococci prevalence was observed in 2018 compared to 2017 (OR = 0.52; 95% CI: 0.30-0.87, p = 0.0106). This effect was larger in the vaccinated compared to the control group (OR = 0.37; 95% CI: 0.12-0.98, p = 0.0368). Interpretation: While deployment of the 4CMenB vaccination did not alter the carriage of hyperinvasive MenB in the vaccinated population, it altered the carriage of other N. meningitidis sequence types following the vaccination program. Our findings suggest 4CMenB vaccination is unlikely to reduce transmission of hyperinvasive N. meningitidis strains and therefore ongoing targeted vaccination is likely a more effective public health intervention. Funding: This work was funded by GlaxoSmithKline Biologicals SA.

Nasopharyngeal Meningococcal Carriage among Children and Adolescents in Turkey in 2018: An Unexpected High Serogroup X Carriage.

Meningococcal carriage studies and transmission modeling can predict IMD epidemiology and used to define invasive meningococcal disease (IMD) control strategies. In this multicenter study, we aimed to evaluate the prevalence of nasopharyngeal Neisseria meningitidis (Nm) carriage, serogroup distribution, and related risk factors in Turkey. Nasopharyngeal samples were collected from a total of 1267 children and adolescents and were tested with rt-PCR. Nm carriage was detected in 96 participants (7.5%, 95% CI 6.1-9.0), with the peak age at 13 years (12.5%). Regarding age groups, Nm carriage rate was 7% in the 0-5 age group, was 6.9%in the 6-10 age group, was 7.9% in the 11-14 age group, and was 9.3% in the 15-18 age group. There was no statistically significant difference between the groups (p > 0.05). The serogroup distribution was as follows: 25% MenX, 9.4% MenA, 9.4% MenB, 2.1% MenC, 3.1% MenW, 2.1% for MenY, and 48.9% for non-groupable. The Nm carriage rate was higher in children with previous upper respiratory tract infections and with a high number of household members, whereas it was lower in children with antibiotic use in the last month (p < 0.05 for all). In this study, MenX is the predominant carriage strain. The geographical distribution of Nm strains varies, but serogroup distribution in the same country might change in a matter of years. Adequate surveillance and/or a proper carriage study is paramount for accurate/dynamic serogroup distribution and the impact of the proposed vaccination.

A Narrative Review of the W, X, Y, E, and NG of Meningococcal Disease: Emerging Capsular Groups, Pathotypes, and Global Control.

Neisseria meningitidis, carried in the human nasopharynx asymptomatically by ~10% of the population, remains a leading cause of meningitis and rapidly fatal sepsis, usually in otherwise healthy individuals. The epidemiology of invasive meningococcal disease (IMD) varies substantially by geography and over time and is now influenced by meningococcal vaccines and in 2020-2021 by COVID-19 pandemic containment measures. While 12 capsular groups, defined by capsular polysaccharide structures, can be expressed by N. meningitidis, groups A, B, and C historically caused most IMD. However, the use of mono-, bi-, and quadrivalent-polysaccharide-conjugate vaccines, the introduction of protein-based vaccines for group B, natural disease fluctuations, new drugs (e.g., eculizumab) that increase meningococcal susceptibility, changing transmission dynamics and meningococcal evolution are impacting the incidence of the capsular groups causing IMD. While the ability to spread and cause illness vary considerably, capsular groups W, X, and Y now cause significant IMD. In addition, group E and nongroupable meningococci have appeared as a cause of invasive disease, and a nongroupable N. meningitidis pathotype of the hypervirulent clonal complex 11 is causing sexually transmitted urethritis cases and outbreaks. Carriage and IMD of the previously "minor" N. meningitidis are reviewed and the need for polyvalent meningococcal vaccines emphasized.

Meningococcal Carriage in 'Men Having Sex With Men' With Pharyngeal Gonorrhoea.

We assessed the characteristics of Neisseria meningitidis pharyngeal carriage in a cohort of 'men having sex with men', including patients with pharyngeal Neisseria gonorrhoeae infection. In the period 2017-2019, among all the oropharyngeal samples tested for gonorrhoea from MSM attending a STI Clinic in Bologna (Italy), we randomly selected 244 N. gonorrhoeae-positive samples and 403 negatives (n=647). Pharyngeal specimens were tested for N. meningitidis presence, by the detection of sodC gene. N. meningitidis-positive samples were further grouped by PCR tests for the major invasive genogroups (i.e., A, B, C, W, and Y). A molecular assay, targeting capsule transporter gene, was used to determine meningococcal capsular status. Overall, 75.8% (491/647) of samples tested positive for sodC gene, indicating a pharyngeal meningococcal carriage. Meningococcal colonisation was significantly more frequent in younger subjects (P=0.009), with no association with HIV infection. Non-groupable meningococci represented most of pharyngeal carriages (about 71%). The commonest N. meningitidis serogroup was B (23.6%), followed by C (2.1%), Y (1.8%) and W (1.1%). Meningococci were often characterized by the genetic potential of capsule production. Interestingly, a negative association between N. meningitidis and N. gonorrhoeae was found: pharyngeal gonorrhoea was significantly more present in patients without meningococcal carriage (P=0.03). Although preliminary, our data added knowledge on the epidemiology of meningococcal carriage in MSM communities at high risk of gonococcal infections, gaining new insights into the interactions/dynamics between N. meningitidis and N. gonorrhoeae.

Molecular insights into meningococcal carriage isolates from Burkina Faso 7 years after introduction of a serogroup A meningococcal conjugate vaccine.

In 2010, Burkina Faso completed the first nationwide mass-vaccination campaign of a meningococcal A conjugate vaccine, drastically reducing the incidence of disease caused by serogroup A meningococci. Since then, other strains, such as those belonging to serogroups W, X and C, have continued to cause outbreaks within the region. A carriage study was conducted in 2016 and 2017 in the country to characterize the meningococcal strains circulating among healthy individuals following the mass-vaccination campaign. Four cross-sectional carriage evaluation rounds were conducted in two districts of Burkina Faso, Kaya and Ouahigouya. Oropharyngeal swabs were collected for the detection of Neisseria meningitidis by culture. Confirmed N. meningitidis isolates underwent whole-genome sequencing for molecular characterization. Among 13 758 participants, 1035 (7.5 %) N. meningitidis isolates were recovered. Most isolates (934/1035; 90.2 %) were non-groupable and primarily belonged to clonal complex (CC) 192 (822/934; 88 %). Groupable isolates (101/1035; 9.8 %) primarily belonged to CCs associated with recent outbreaks in the region, such as CC11 (serogroup W) and CC10217 (serogroup C); carried serogroup A isolates were not detected. Phylogenetic analysis revealed several CC11 strains circulating within the country, several of which were closely related to invasive isolates. Three sequence types (STs) were identified among eleven CC10217 carriage isolates, two of which have caused recent outbreaks in the region (ST-10217 and ST-12446). Our results show the importance of carriage studies to track the outbreak-associated strains circulating within the population in order to inform future vaccination strategies and molecular surveillance programmes.

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

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

Pharyngeal carriage rates of Neisseria meningitidis in health care professionals at a tertiary university pediatric hospital.

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.

Meningococcal and pneumococcal carriage in Hajj pilgrims: findings of a randomized controlled trial.

BACKGROUND: Intense congestion during the Hajj pilgrimage amplifies the risk of meningococcal carriage and disease, and there have been many meningococcal outbreaks reported amongst pilgrims. Thus, a strict vaccination policy is enforced by the host country and either polysaccharide or conjugate quadrivalent meningococcal vaccines are mandatory. However, unlike conjugate vaccines, the polysaccharide vaccine is not thought to reduce pharyngeal carriage of meningococci. METHODS: A single-blinded, randomized, controlled trial amongst pilgrims from Saudi Arabia and Australia during the Hajj seasons of 2016-2017 was conducted to compare MenACWY-Conjugate vaccine with MenACWY-Polysaccharide vaccine, to determine if the conjugate vaccine is more effective in reducing asymptomatic carriage of meningococci, and whether the effect may be long-standing. Oropharyngeal swabs were obtained pre-, immediately post- and 6-11 months following completion of Hajj and tested for the presence of meningococci. RESULTS: Amongst 2000 individuals approached, only 1146 participants aged 18-91 (mean 37.6) years agreed to participate and were randomized to receive either the polysaccharide (n = 561) or the conjugate (n = 561) vaccine, 60.8% were male, and 93.5% were from Saudi Arabia. Amongst oropharyngeal swabs obtained before Hajj, only two (0.2%) tested positive for Neisseria meningitidis. Similarly, meningococci were identified in only one sample at each of the post-Hajj and late follow-up visits. None of the carriage isolates were amongst the serogroups covered by the vaccines. A post hoc analysis of the third swabs revealed that 22.4% of all participants (50/223) were positive for Streptococcus pneumoniae nucleic acid. CONCLUSION: The low overall carriage rate of meningococci found amongst Hajj pilgrims in 2016 and 2017 demonstrates a successful vaccination policy, but neither supports nor refutes the superiority of meningococcal conjugate ACWY vaccine over the polysaccharide vaccine against carriage. Although an association could not be established in this study, molecular epidemiology would help to establish the role of Hajj in facilitating transmission of pneumococci and inform vaccination policy.

UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence.

Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999.  The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here.

Narrative review of methods and findings of recent studies on the carriage of meningococci and other Neisseria species in the African Meningitis Belt.

OBJECTIVE: To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007. METHODS: PubMed and Web of Science were searched in July 2018 using the terms 'meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa', with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications. RESULTS: One hundred and thirteen papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVacR ) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI: 3.4%, 6.8%] and that of capsulated N. meningitidis was 2.8% [95% CI: 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad. CONCLUSIONS: Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries.

Prevalence of meningococcal carriage among male university students living in dormitories in Kerman, southeast of Iran.

Neisseria meningitidis is an important causative agent of bacterial meningitis. The nasopharynx is the only known reservoir of this organism. Although the relationship between carriage and invasive disease is not completely understood, asymptomatic meningococcal carriers are considered as the most important sources for causing strains of disease. Living in closed and overcrowded places such as university dormitories can increase the carriage rate and meningococcal disease. This cross-sectional study was conducted to determine the prevalence of N. meningitidis carriers among male students living in three dormitories affiliated with Kerman University of Medical Sciences (Kerman, Iran). Nasopharyngeal swab was taken from all participants recruited in the study. Conventional microbiological tests were performed for isolation and detection of the organism. The amplification of crgA gene was used to confirm the identity of isolates. Molecular serogrouping was used to detect the six most frequent serotypes. The overall carriage rate was 6.8% (23/335). The capsular type of these isolates was in determinate (56.5%) or of serogroup C (43.5%). Multivariate logistic regression analysis revealed that cigarette smoking was significantly associated with meningococcal carriage (OR = 5.02; p = 0.01). Additionally, using univariate regression analysis, a significant association was found between water pipe smoking and carriage (p = 0.018). The rate of meningococcal carriage among male students in the studied population was lower as compared to other high-risk group (freshmen conscripts) in Iran. University students should be aware of the consequences of cigarette and water pipe smoking as risk factors in meningococcal carriage.

An unwanted guest: Neisseria meningitidis - carriage, risk for invasive disease and the impact of vaccination with insight on Italy incidence.

INTRODUCTION: Invasive Meningococcal Disease (IMD) represents a potentially life-threatening condition caused by Neisseria meningitidis. The disease is characterized by a case fatality rate of 5-10% whereas serious clinical sequelae can develop in survivors within 12-24 h from the first symptoms. However, IMD infection only occurs rarely, in fact, most of the interactions established between N. meningitidis and the host are harmless, and an estimated 10% of the population asymptomatically carries the bacterium in the nasopharynx. Meningococcal carriage represents a critical condition for IMD onset since it represents the first step for disease transmission. Furthermore, high levels of carriage can promote genetic recombination among different N. meningitidis strains potentially leading to the development of new pathogenic variants. Areas covered: The present review discusses N. meningitidis carriage, factors able to influence meningococcal carriage and disease and the effect of vaccinations on both conditions, with a particular focus on Italy. Expert commentary: Data regarding the effect of different meningococcal vaccines on N. meningitidis carriage are available, whereas further studies are needed to investigate the positive impact of the two recently licensed vaccines 4CMenB and rLP2086 on meningococcal carriage.

Fast and accurate dynamic estimation of field effectiveness of meningococcal vaccines.

BACKGROUND: Estimating the effectiveness of meningococcal vaccines with high accuracy and precision can be challenging due to the low incidence of the invasive disease, which ranges between 0.5 and 1 cases per 100,000 in Europe and North America. Vaccine effectiveness (VE) is usually estimated with a screening method that combines in one formula the proportion of meningococcal disease cases that have been vaccinated and the proportion of vaccinated in the overall population. Due to the small number of cases, initial point estimates are affected by large uncertainties and several years may be required to estimate VE with a small confidence interval. METHODS: We used a Monte Carlo maximum likelihood (MCML) approach to estimate the effectiveness of meningococcal vaccines, based on stochastic simulations of a dynamic model for meningococcal transmission and vaccination. We calibrated the model to describe two immunization campaigns: the campaign against MenC in England and the Bexsero campaign that started in the UK in September 2015. First, the MCML method provided estimates for both the direct and indirect effects of the MenC vaccine that were validated against results published in the literature. Then, we assessed the performance of the MCML method in terms of time gain with respect to the screening method under different assumptions of VE for Bexsero. RESULTS: MCML estimates of VE for the MenC immunization campaign are in good agreement with results based on the screening method and carriage studies, yet characterized by smaller confidence intervals and obtained using only incidence data collected within 2 years of scheduled vaccination. Also, we show that the MCML method could provide a fast and accurate estimate of the effectiveness of Bexsero, with a time gain, with respect to the screening method, that could range from 2 to 15 years, depending on the value of VE measured from field data. CONCLUSIONS: Results indicate that inference methods based on dynamic computational models can be successfully used to quantify in near real time the effectiveness of immunization campaigns against Neisseria meningitidis. Such an approach could represent an important tool to complement and support traditional observational studies, in the initial phase of a campaign.

Prevalence of meningococcal carriage in children and adolescents aged 10-19 years in Chile in 2013.

In 2011, Chile experienced an increase in the number of cases of IMD caused by Neisseria meningitidis group W. This epidemiological scenario prompted authorities to implement prevention strategies. As part of these strategies, the Institute of Public Heath of Chile conducted a cross-sectional study to determine the prevalence of pharyngeal carriage of N. meningitidis in a representative sample of healthy children and adolescents aged 10-19 years. The identification of presumptive N. meningitidis strains was performed by testing carbohydrate utilization in the National Reference Laboratory at the ISP. Association of meningococcal carriage with risk factors was analyzed by calculating the Odds Ratio. Selected variables were included in a logistic model for risk analyses. The prevalence of carriage of N. meningitidis was 6.5% (CI: 5.7-7.3%). Older age (carriers: 14.2±0.29 vs. non-carriers: 13.8±0.08 years old; p=0.009), cohabitation with children (carriers: 0.9±0.13 vs. non-carriers: 0.7±0.03; p=0.028), number of smoking cohabitants (carriers: 0.55±0.13 vs. non-carriers: 0.44±0.03) and frequent attendance to crowded social venues (carriers: 49% vs. non-carriers: 37%; p=0.008) were determined to favor carriage. Statistical modeling showed that meningococcal carriage was associated with older age (OR: 1.077, p-value: 0.002) and cohabitation with children (OR: 1.182, p-value: 0.02).

Serogroup A meningococcal conjugate vaccines in Africa.

Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa.

Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study.

BACKGROUND: Herd protection by meningococcal vaccines is conferred by population-level reduction of meningococcal nasopharyngeal colonization. Given the inverse epidemiological association between colonization by commensal Neisseria lactamica and meningococcal disease, we investigated whether controlled infection of human volunteers with N. lactamica prevents colonization by Neisseria meningitidis. METHODS: In a block-randomized human challenge study, 310 university students were inoculated with 10(4) colony-forming units of N. lactamica or were sham-inoculated, and carriage was monitored for 26 weeks, after which all participants were reinoculated with N. lactamica and resampled 2 weeks later. RESULTS: At baseline, natural N. meningitidis carriage in the control group was 22.4% (36/161), which increased to 33.6% (48/143) by week 26. Two weeks after inoculation of N. lactamica, 33.6% (48/143) of the challenge group became colonized with N. lactamica. In this group, meningococcal carriage reduced from 24.2% (36/149) at inoculation to 14.7% (21/143) 2 weeks after inoculation (-9.5%; P = .006). The inhibition of meningococcal carriage was only observed in carriers of N. lactamica, was due both to displacement of existing meningococci and to inhibition of new acquisition, and persisted over at least 16 weeks. Crossover inoculation of controls with N. lactamica replicated the result. Genome sequencing showed that inhibition affected multiple meningococcal sequence types. CONCLUSIONS: The inhibition of meningococcal carriage by N. lactamica is even more potent than after glycoconjugate meningococcal vaccination. Neisseria lactamica or its components could be a novel bacterial medicine to suppress meningococcal outbreaks. This observation explains the epidemiological observation of natural immunity conferred by carriage of N. lactamica. CLINICAL TRIALS REGISTRATION: NCT02249598.

Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010.

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.