This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of β-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI.

Objectives Systematically review the evidence on the association between active and passive tobacco smoking and invasive meningococcal disease (IMD) in adolescents and young adults aged 15-to-24-years. Methods Electronic searches were conducted in Ovid MEDLINE, EMBASE, and Web of Science to June 2020. Reference lists were hand-searched. Two independent reviewers screened articles for eligibility. Risk of bias was assessed using an adapted Risk of Bias in Non-Randomised Studies - of Interventions tool. Meta-analyses were conducted using random-effects models. Results Of 312 records identified, 13 studies were included. Five studies provided data on the association between active smoking and IMD in the target age group; pooled odds ratio (OR): 1.45 (95% CI: 0.93–2.26). The overall OR, including eight studies with a wider participant age range, was 1.45 (95% CI: 1.12–1.88). For passive smoking, the equivalent ORs were 1.56 (95% CI: 1.09–2.25) and 1.30 (95% CI: 1.06–1.59) respectively. All studies were at high risk of bias. Conclusions Active and passive smoking may be associated with IMD in adolescents and young adults. Since active smoking has also been linked to meningococcal carriage, and passive smoking to IMD in young children, smoking cessation should be encouraged to reduce transmission and IMD risk in all ages.

The World Health Organization (WHO) has developed a global roadmap to defeat meningitis by 2030. To advocate for and track progress of the roadmap, the burden of meningitis as a syndrome and by pathogen must be accurately defined. Three major global health models estimating meningitis mortality as a syndrome and/or by causative pathogen were identified and compared for the baseline year 2015. Two models, (1) the WHO and the Johns Hopkins Bloomberg School of Public Health’s Maternal and Child Epidemiology Estimation (MCEE) group’s Child Mortality Estimation (WHO-MCEE) and (2) the Institute for Health Metrics and Evaluation (IHME) Global Burden of Disease Study (GBD 2017), identified meningitis, encephalitis and neonatal sepsis, collectively, to be the second and third largest infectious killers of children under five years, respectively. Global meningitis/encephalitis and neonatal sepsis mortality estimates differed more substantially between models than mortality estimates for selected infectious causes of death and all causes of death combined. Estimates at national level and by pathogen also differed markedly between models. Aligning modelled estimates with additional data sources, such as national or sentinel surveillance, could more accurately define the global burden of meningitis and help track progress against the WHO roadmap.

Bacterial meningitis has serious health, economic, and social consequences with a high risk of death and lifelong disability. [...]

Objectives: Systematically review the evidence on the association between active and passive tobacco smoking and invasive meningococcal disease (IMD) in adolescents and young adults aged 15-to-24-years. Methods: Electronic searches were conducted in Ovid MEDLINE, EMBASE, and Web of Science to June 2020. Reference lists were hand-searched. Two independent reviewers screened articles for eligibility. Risk of bias was assessed using an adapted Risk of Bias in Non-Randomised Studies - of Interventions tool. Meta-analyses were conducted using random-effects models. Results: Of 312 records identified, 13 studies were included. Five studies provided data on the association between active smoking and IMD in the target age group; pooled odds ratio (OR): 1.45 (95% CI: 0.93-2.26). The overall OR, including eight studies with a wider participant age range, was 1.45 (95% CI: 1.12-1.88). For passive smoking, the equivalent ORs were 1.56 (95% CI: 1.09-2.25) and 1.30 (95% CI: 1.06-1.59) respectively. All studies were at high risk of bias. Conclusions: Active and passive smoking may be associated with IMD in adolescents and young adults. Since active smoking has also been linked to meningococcal carriage, and passive smoking to IMD in young children, smoking cessation should be encouraged to reduce transmission and IMD risk in all ages. (C) 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.

Objective To investigate potential risk factors for acquisition in seven countries of the meningitis belt. Methods Households were followed up every 2 weeks for 2 months, then monthly for a further 4 months. Pharyngeal swabs were collected from all available household members at each visit and questionnaires completed. Risks of acquisition over the whole study period and for each visit were analysed by a series of logistic regressions. Results Over the course of the study, acquisition was higher in: (i) 5-to 14-year olds, as compared with those 30 years or older (OR 3.6, 95% CI 1.4-9.9); (ii) smokers (OR 3.6, 95% CI 0.98-13); and (iii) those exposed to wood smoke at home (OR 2.6 95% CI 1.3-5.6). The risk of acquisition from one visit to the next was higher in those reporting a sore throat during the dry season (OR 3.7, 95% CI 2.0-6.7) and lower in those reporting antibiotic use (OR 0.17, 95% CI 0.03-0.56). Conclusions Acquisition of meningococcal carriage peaked in school age children. Recent symptoms of sore throat during the dry season, but not during the rainy season, were associated with a higher risk of acquisition. Upper respiratory tract infections may be an important driver of epidemics in the meningitis belt.

Streptococcus pneumoniae is increasingly recognised as an important cause of bacterial meningitis in the African meningitis belt. The World Health Organization sets guidelines for response to outbreaks of meningococcal meningitis, but there are no current guidelines for outbreaks where S. pneumoniae is implicated. We aimed to evaluate the impact of using a similar response to target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis belt. Here, we adapt a previous model of reactive vaccination for meningococcal outbreaks to estimate the potential impact of reactive vaccination in a recent pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using weekly line list data on all suspected cases over a period of five months. We determine the sensitivity and specificity of various epidemic thresholds and model the cases and deaths averted by reactive vaccination. An epidemic threshold of 10 suspected cases per 100,000 population per week performed the best, predicting large outbreaks with 100% sensitivity and more than 85% specificity. In this outbreak, reactive vaccination would have prevented a lower number of cases per individual vaccinated (approximately 15,300 doses per case averted) than previously estimated for meningococcal outbreaks. Since the burden of death and disability from pneumococcal meningitis is higher than that from meningococcal meningitis, there may still be merit in considering reactive vaccination for outbreaks of pneumococcal meningitis. More outbreak data are needed to refine our model estimates. Whatever policy is followed, we emphasize the importance of timely laboratory confirmation of suspected cases to enable appropriate decisions about outbreak response.

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 (MenAfriVac(R)) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from 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((R)) 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.

A large international response was needed to bring the 2014/15 West African Ebola virus disease outbreak under control. This study sought to learn lessons from this epidemic to strengthen the response to future outbreaks of international significance by identifying priorities for future epidemiology training and response. Epidemiologists who were deployed to West Africa were recruited through a snowball sampling method and surveyed using an online anonymous questionnaire. Associations between demographics, training, qualifications, and role while in-country were explored alongside respondents' experience during deployment. Of 128 responses, 105 met the inclusion criteria. Respondents originated from 25 countries worldwide, for many (62%), this was their first deployment abroad. The most common tasks carried out while deployed were surveillance, training, contact tracing, and cluster investigation. Epidemiologists would value more detailed predeployment briefings including organizational aspects of the response. Gaps in technical skills reported were mostly about geographical information systems; however, epidemiologists identified the need for those deployed in future to have greater knowledge about roles and responsibilities of organizations involved in the response, better cultural awareness, and leadership and management skills. Respondents felt that the public health community must improve the timeliness of the response in future outbreaks and strengthen collaboration and coordination between organizations.

The introduction of a serogroup A meningococcal conjugate vaccine in the African meningitis belt has been a remarkable success. Meningitis due to the serogroup A meningococcus, previously responsible for most epidemics, has fallen by 99% in vaccinated countries. Success must, however, not distract from the continuing burden of meningitis in this region of Africa. The number of all meningitis epidemics at health district level has fallen by 60% following vaccination, but epidemics due to other meningococcal serogroups continue and may be increasing. The introduction of low cost multivalent conjugate vaccines must be given high public health priority.

The WHO Strategic Advisory Group of Experts is reviewing the technical evidence to inform policy on optimal use of infant pneumococcal conjugate vaccines (PCV) 1. Since 2010, multivalent vaccines (PCV-10, PCV-13) have been successfully introduced with the support of Gavi, the Vaccine Alliance into infant immunisation programmes across the developing world 2. One recommended schedule consists of three doses under the age of 6 months (3 + 0), with the aim of providing maximum protection to infants, the age group at highest risk of pneumococcal disease 3. An alternative schedule consists of two vaccine doses under the age of 6 months with a booster at 9–15 months (2 + 1). This schedule may have more impact on reducing carriage and transmission of vaccine serotypes to unvaccinated individuals, leading to indirect or herd protection. The question around the most cost-effective policy to achieve both direct and indirect protection has particular importance for the meningitis belt of sub-Saharan Africa. The launch of mass campaigns with a serogroup A conjugate vaccine (MenAfriVacR) across the meningitis belt in 2010 saw a dramatic fall in the incidence of meningitis due to serogroup A, while meningitis due to other meningococcal serogroups and Streptococcus pneumoniae has become more prominent 4. Recent publications from the meningitis belt emphasise the continuing burden of pneumococcal meningitis among older children and adults in this region. In Ghana, a large outbreak occurred in 2016 with close to 900 suspected cases and 104 cases confirmed as due to S. pneumoniae, mainly serotype 1, with a median age of 20 years, in part of the country adjoining the meningitis belt 5. In Burkina Faso from 2011 to 13, 1528 (53%) of 2858 cases of laboratory confirmed bacterial meningitis was due to S. pneumoniae, also mainly serotype 1 6. The proportion of cases aged over 5 years was 95% in Ghana and 69% in Burkina Faso. PCV programmes that started in 2013 in Ghana likely protected young children in the 2016 outbreak, whereas the Burkina Faso data were taken from the years preceding PCV vaccination. Bacterial meningitis due to S. pneumoniae has a remarkably high case fatality ratios in sub-Saharan Africa 7 and causes much disability in survivors 8. A systematic review of paediatric meningitis in children in Africa found among cases of confirmed pneumococcal meningitis that the median in-hospital case fatality ratio was 35% and that 25% of survivors had in-hospital sequelae, these figures being 9× and 4× higher respectively than those for meningococcal meningitis 8. Incidence of pneumococcal meningitis is particularly high in the meningitis belt, with a similar seasonality to meningococcal meningitis, consistent with similar predisposing environmental factors 7, 9. Reducing the burden of pneumococcal meningitis in these countries should be given high public health priority. For outbreak control, pneumococcal vaccines could potentially be given to children and adults in reactive mass campaigns, a similar strategy to that using meningococcal vaccines for controlling outbreaks of meningococcal meningitis 10. However, reactive vaccination for meningococcal meningitis is resource intensive and relatively ineffective unless undertaken promptly 11, 12, and effectiveness of such a policy in controlling outbreaks of pneumococcal meningitis is not known 13. Preventive vaccination offers more hope. Even though serotype 1 is rarely found in carriage isolates, evidence of indirect protection against serotype 1 was found in South Africa after introduction of a 2 + 1 PCV-13 infant vaccination schedule 14. How best can we achieve indirect protection of older age groups at high risk of pneumococcal meningitis in the meningitis belt? Inclusion of a booster dose may be more important for some serotypes, including serotype 1 15, and extended vaccination among children up to the age of 5 years, in whom carriage prevalence is highest in sub-Saharan Africa 16, may increase effectiveness 2, 17. A 3 + 0 schedule supplemented by a catch-up campaign to the age of 5 years in Kenya reduced carriage of vaccine serotypes in vaccinated and unvaccinated age groups 18. In contrast, a study from the Gambia showed no evidence as yet of a reduction in serotype 1 disease in persons aged >5 years after introducing a 3 + 0 PCV-13 schedule without catch-up in 2011 19, and the pneumococcal meningitis outbreak this year in Ghana occurred despite the prior introduction of a 3 + 0 schedule with high coverage in the two previous years. Most countries of the meningitis belt have introduced a 3 + 0 schedule. Switching to a 2 + 1 schedule with a single dose catch-up in children up to 5 years of age could extend individual protection, lead to a higher level of indirect protection and lower the risk of outbreaks from this devastating disease.

Background Serogroup A Neisseria meningitidis ( Nm A) 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 Nm A isolates. Results All 23 Nm A isolates belonged to the ST-5 clonal complex (cc5). Ribosomal MLST comparison with other publically available Nm A:cc5 showed that isolates were closely related, although those from Chad formed two distinct branches and did not cluster with other Nm A, 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 Nm A 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.

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.

Background In preparation for the introduction of MenAfriVac, a meningococcal group A conjugate vaccine developed for the African meningitis belt, an enhanced meningitis surveillance network was established. We analysed surveillance data on suspected and confirmed cases of meningitis to quantify vaccine impact.Methods We compiled and analysed surveillance data for nine countries in the meningitis belt (Benin, Burkina Faso, Chad, Cote d'Ivoire, Ghana, Mali, Niger, Nigeria, and Togo) collected and curated by the WHO Inter-country Support Team between 2005 and 2015. The incidence rate ratios (IRRs) of suspected and confirmed cases in vaccinated and unvaccinated populations were estimated with negative binomial regression models. The relative risk of districts reaching the epidemic threshold of ten per 100 000 per week was estimated according to district vaccination status.Findings The incidence of suspected meningitis cases declined by 57% (95% CI 55-59) in vaccinated compared with unvaccinated populations, with some heterogeneity observed by country. We observed a similar 59% decline in the risk of a district reaching the epidemic threshold. In fully vaccinated populations, the incidence of confirmed group A disease was reduced by more than 99%. The IRR for non-A serogroups was higher after completion of MenAfriVac campaigns (IRR 2.76, 95% CI 1.21-6.30).Interpretation MenAfriVac introduction has led to substantial reductions in the incidence of suspected meningitis and epidemic risk, and a substantial effect on confirmed group A meningococcal meningitis. It is important to continue strengthening surveillance to monitor vaccine performance and remain vigilant against threats from other meningococcal serogroups and other pathogens.

Background Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known. Methods Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period. Results Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up. Conclusion Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.