Impact of meningococcal ACWY conjugate vaccines on pharyngeal carriage in adolescents: evidence for herd protection from the UK MenACWY programme.

OBJECTIVE: Serogroup W and Y invasive meningococcal disease increased globally from 2000 onwards. Responding to a rapid increase in serogroup W clonal complex 11 (W:cc11) invasive meningococcal disease, the UK replaced an adolescent booster dose of meningococcal C conjugate vaccine with quadrivalent MenACWY conjugate vaccine in 2015. By 2018, the vaccine coverage in the eligible school cohorts aged 14 to 19 years was 84%. We assessed the impact of the MenACWY vaccination programme on meningococcal carriage. METHODS: An observational study of culture-defined oropharyngeal meningococcal carriage prevalence before and after the start of the MenACWY vaccination programme in UK school students, aged 15 to 19 years, using two cross-sectional studies: 2014 to 2015 "UKMenCar4" and 2018 "Be on the TEAM" (ISRCTN75858406). RESULTS: A total of 10 625 participants preimplementation and 13 438 postimplementation were included. Carriage of genogroups C, W, and Y (combined) decreased from 2.03 to 0.71% (OR 0.34 [95% CI 0.27-0.44], p < 0.001). Carriage of genogroup B meningococci did not change (1.26% vs 1.23% [95% CI 0.77-1.22], p = 0.80) and genogroup C remained rare (n = 7/10 625 vs 17/13 438, p = 0.135). The proportion of serogroup positive isolates (i.e. those expressing capsule) decreased for genogroup W by 53.8% (95% CI -5.0 - 79.8, p = 0.016) and for genogroup Y by 30.1% (95% CI 8.946·3, p = 0.0025). DISCUSSION: The UK MenACWY vaccination programme reduced carriage acquisition of genogroup and serogroup Y and W meningococci and sustained low levels of genogroup C carriage. These data support the use of quadrivalent MenACWY conjugate vaccine for indirect (herd) protection.

Meningococcal carriage among Hajj pilgrims, risk factors for carriage and records of vaccination: a study of pilgrims to Mecca.

OBJECTIVE: The Saudi government requires that all pilgrims receive a quadrivalent meningococcal vaccine at least 10 days before the Hajj. We conducted a study to determine the uptake of meningococcal vaccine and antibiotic use. We also investigated risk factors of meningococcal carriage and carriage of Neisseria meningitidis pathogenic serogroups A, C, W and Y. METHODS: A cross-sectional oropharyngeal carriage survey was conducted in 2973 Hajj pilgrims in September 2017. A real-time polymerase chain reaction (rt-PCR) assay was used to identify N. meningitidis from the oropharyngeal swabs. A questionnaire investigated potential risk factors for carriage of N. meningitidis. RESULTS: Two thousand two hundred forty nine oropharyngeal swabs were obtained. The overall prevalence of carriage of N. meningitidis was 4.6% (95% CI: 3.4%-6%). Carriage of pathogenic serogroups was not associated significantly with any of the meningococcal risk factors evaluated. 77% of pilgrims were vaccinated but 22.58 % said they were carrying unofficial vaccination cards. CONCLUSION: Carriage of serogroups A, C, W and Y was not significantly associated with any of the risk factors investigated. Almost a quarter of pilgrims were unlikely to have been vaccinated, highlighting a need to strengthen compliance with the current policy of vaccination to prevent meningococcal disease outbreaks during and after the Hajj.

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 carriage by age in the African meningitis belt: a systematic review and meta-analysis.

Meningococcal carriage dynamics drive patterns of invasive disease. The distribution of carriage by age has been well described in Europe, but not in the African meningitis belt, a region characterised by frequent epidemics of meningitis. We aimed to estimate the age-specific prevalence of meningococcal carriage by season in the African meningitis belt. We searched PubMed, Web of Science, the Cochrane Library and grey literature for papers reporting carriage of Neisseria meningitidis in defined age groups in the African meningitis belt. We used a mixed-effects logistic regression to model meningococcal carriage prevalence as a function of age, adjusting for season, location and year. Carriage prevalence increased from low prevalence in infants (0.595% in the rainy season, 95% CI 0.482-0.852%) to a broad peak at age 10 (1.94%, 95% CI 1.87-2.47%), then decreased in adolescence. The odds of carriage were significantly increased during the dry season (OR 1.5 95% CI 1.4-1.7) and during outbreaks (OR 6.7 95% CI 1.6-29). Meningococcal carriage in the African meningitis belt peaks at a younger age compared to Europe. This is consistent with contact studies in Africa, which show that children 10-14 years have the highest frequency of contacts. Targeting older children in Africa for conjugate vaccination may be effective in reducing meningococcal transmission.

Respiratory carriage of the novel Kingella negevensis species by young children.

Kingella negevensis, a novel Kingella species implicated in a pediatric joint infection, has been recently characterized but its epidemiology remains largely unknown. The pharyngeal carriage of K. negevensis was studied by re-examining the results of a previous longitudinal study conducted in a cohort of healthy Israeli children from whom upper respiratory tract specimens were sequentially cultured between the ages of 2 and 36 months. Isolates were identified as K. negevensis by a species-specific nucleic amplification assay and genotyped by pulsed-field gel electrophoresis. ß-lactamase production was determined by the nitrocephin test. Kingella negevensis was detected in 26 of 4,472 (0.58%) oropharyngeal cultures obtained from 24 of 716 children (3.35%) and was not isolated from any of 4,472 nasopharyngeal specimens. Following the first 6 months of life during which none of the children was colonized, the prevalence of carriage gradually increased reaching a peak of 1.09% at 24 months of age and decreased thereafter. Kingella negevensis strains showed genomic heterogeneity, and two clones represented 22 of 26 (84.62%) isolates. Twelve of the 26 (46.15%) isolates, belonging to two distinct clones, produced ß-lactamase. Kingella negevensis shows remarkable similarities with K. kingae in terms of colonization site, age-related patterns of acquisition and carriage, and clonal distribution of ß-lactamase production. Additional research is needed to investigate potential colonization sites of K. negevensis outside the respiratory tract, explore the mechanisms of pharyngeal colonization by the organism, and determine its role as an invasive human pathogen.

Management of children with persistent group A streptococcal carriage.

INTRODUCTION: Chronic GAS carrier state is best defined as the prolonged presence of group A ß-haemolytic Streptococcus (GAS) in the pharynx without evidence of infection or inflammation. Chronic GAS carriers have a low risk of immune mediated complications. Persistent pharyngeal carriage often raises management issues. In this study, we review the evidence on the management of persistent GAS carriage in children and propose a management algorithm. Areas covered: Chronic GAS pharyngeal carriage is quite common affecting 10-20% of school-aged children. Pathogenesis of carriage has been related to the pharynx microflora and to special properties of GAS, but several aspects are yet to be elucidated. Management greatly depends on whether the individual child belongs to a 'high-risk' group and might benefit from eradication regimens or not, when observation-only and reassurance are enough. Penicillin plus rifampin and clindamycin monotherapy have been recommended for eradication; limited evidence of effectiveness of azithromycin has been reported. Surgical intervention is not indicated. Expert commentary: GAS infection is a common reason for antibiotic use and abuse in children and asymptomatic carriers constitute the major reservoir of GAS in the community. Several aspects are yet to be elucidated and well-designed studies are needed for firm conclusions to be drawn.

Hierarchical genomic analysis of carried and invasive serogroup A Neisseria meningitidis during the 2011 epidemic in Chad.

BACKGROUND: Serogroup A Neisseria meningitidis (NmA) was the cause of the 2011 meningitis epidemics in Chad. This bacterium, often carried asymptomatically, is considered to be an "accidental pathogen"; however, the transition from carriage to disease phenotype remains poorly understood. This study examined the role genetic diversity might play in this transition by comparing genomes from geographically and temporally matched invasive and carried NmA isolates. RESULTS: All 23 NmA isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available NmA:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other NmA, based on their MLST profile, geographical and temporal location. Whole genome MLST (wgMLST) comparison identified 242 variable genes among all Chadian isolates and clustered them into three distinct phylogenetic groups (Clusters 1, 2, and 3): no systematic clustering by disease or carriage source was observed. There was a significant difference (p = 0.0070) between the mean age of the individuals from which isolates from Cluster 1 and Cluster 2 were obtained, irrespective of whether the person was a case or a carrier. CONCLUSIONS: Whole genome sequencing provided high-resolution characterization of the genetic diversity of these closely related NmA isolates. The invasive meningococcal isolates obtained during the epidemic were not homogeneous; rather, a variety of closely related but distinct clones were circulating in the human population with some clones preferentially colonizing specific age groups, reflecting a potential age-related niche adaptation. Systematic genetic differences were not identified between carriage and disease isolates consistent with invasive meningococcal disease being a multi-factorial event resulting from changes in host-pathogen interactions along with the bacterium.

Neisseria models of infection and persistence in the upper respiratory tract.

The Gram-negative bacteria genus Neisseria includes both pathogenic and commensal species that are found primarily in the upper respiratory tract of humans and animals. The development of animal models to study neisserial pathogenesis has focused almost exclusively on two species that cause disease in humans. These include Neisseria meningitidis, an obligate commensal that can cause invasive disease, and N. gonorrhoeae, the causative agent of gonorrhea. Both pathogens can persist in the upper respiratory tract. This article will give a brief overview of the genus Neisseria. The anatomy of the upper respiratory tract and its use as a niche for bacteria will be discussed. Next, studies that provide insight about the first stage of upper respiratory tract infection, namely colonization, will be reviewed. Most studies of upper respiratory tract infection have focused on N. meningitidis infections of laboratory mice. This review will also discuss models of respiratory tract persistence by Neisseria species, including commensals, in mice, non-human primates and human volunteers. The article includes a section that discusses the future utility of upper respiratory tract models in informing the development of effective antimicrobial therapies. Such knowledge is needed to minimize the dissemination of antimicrobial resistance from respiratory reservoirs.

Pneumococcus and the Elderly in Italy: A Summary of Available Evidence Regarding Carriage, Clinical Burden of Lower Respiratory Tract Infections and On-Field Effectiveness of PCV13 Vaccination.

Streptococcus pneumoniae is currently the leading cause of community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) in adults, elderly and high-risk subjects worldwide. The clear benefits of pneumococcal conjugate vaccination in childhood have been accompanied by a decrease of vaccine-serotype invasive diseases among adults in several countries, mainly due to the herd effect mediated by the reduction of vaccine-serotype nasopharyngeal colonization in both age groups, but this reduction in the incidence of pneumonia has not been observed. The "Community Acquired Pneumonia Immunization Trial in Adults" (CAPITA) study provided conclusive evidence about 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing CAP in adults and led Western countries to issue new recommendations for pneumococcal immunization targeting subjects >50 years and high-risk groups, with marked differences with respect to age and/or risk groups immunized, eligibility for reimbursement and national, regional or local implementation. Several Italian regions implemented PCV13 immunization programs in adults and interesting data have been come available in the last years, especially from Liguria, a Northern region with a high and long-lasting pneumococcal vaccine immunological pressure in infants. In this review, currently available evidence from Italy and Liguria regarding pneumococcal carriage, burden of CAP and LRTI, and on-field effectiveness of PCV13 immunization in adults and elderly will be summarized.

Pharyngeal carriage of Neisseria species in the African meningitis belt.

OBJECTIVES: Neisseria meningitidis, together with the non-pathogenic Neisseria species (NPNs), are members of the complex microbiota of the human pharynx. This paper investigates the influence of NPNs on the epidemiology of meningococcal infection. METHODS: Neisseria isolates were collected during 18 surveys conducted in six countries in the African meningitis belt between 2010 and 2012 and characterized at the rplF locus to determine species and at the variable region of the fetA antigen gene. Prevalence and risk factors for carriage were analyzed. RESULTS: A total of 4694 isolates of Neisseria were obtained from 46,034 pharyngeal swabs, a carriage prevalence of 10.2% (95% CI, 9.8-10.5). Five Neisseria species were identified, the most prevalent NPN being Neisseria lactamica. Six hundred and thirty-six combinations of rplF/fetA_VR alleles were identified, each defined as a Neisseria strain type. There was an inverse relationship between carriage of N. meningitidis and of NPNs by age group, gender and season, whereas carriage of both N. meningitidis and NPNs was negatively associated with a recent history of meningococcal vaccination. CONCLUSION: Variations in the prevalence of NPNs by time, place and genetic type may contribute to the particular epidemiology of meningococcal disease in the African meningitis belt.