Meningococcal disease in North America: Updates from the Global Meningococcal Initiative.

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 ß-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.

The Global Burden of Meningitis in Children: Challenges with Interpreting Global Health Estimates.

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.

Next generation rapid diagnostic tests for meningitis diagnosis.

Rapid diagnostic tests (RDTs) are increasingly recognized as valuable, transformative tools for the diagnosis of infectious diseases. Although there are a variety of meningitis RDTs currently available, certain product features restrict their use to specific levels of care and settings. For this reason, the development of meningitis RDTs for use at all levels of care, including those in low-resource settings, was included in the "Defeating Meningitis by 2030" roadmap. Here we address the limitations of available meningitis RDTs and present test options and specifications to consider when developing the next generation of meningitis RDTs.

The global meningitis genome partnership.

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.

Economic evaluation of meningococcal vaccines: considerations for the future.

In 2018, a panel of health economics and meningococcal disease experts convened to review methodologies, frameworks, and decision-making processes for economic evaluations of vaccines, with a focus on evaluation of vaccines targeting invasive meningococcal disease (IMD). The panel discussed vaccine evaluation methods across countries; IMD prevention benefits that are well quantified using current methods, not well quantified, or missing in current cost-effectiveness methodologies; and development of recommendations for future evaluation methods. Consensus was reached on a number of points and further consideration was deemed necessary for some topics. Experts agreed that the unpredictability of IMD complicates an accurate evaluation of meningococcal vaccine benefits and that vaccine cost-effectiveness evaluations should encompass indirect benefits, both for meningococcal vaccines and vaccines in general. In addition, the panel agreed that transparency in the vaccine decision-making process is beneficial and should be implemented when possible. Further discussion is required to ascertain: how enhancing consistency of frameworks for evaluating outcomes of vaccine introduction can be improved; reviews of existing tools used to capture quality of life; how indirect costs are considered within models; and whether and how the weighting of quality-adjusted life-years (QALY), application of QALY adjustment factors, or use of altered cost-effectiveness thresholds should be used in the economic evaluation of vaccines.

Toward a Global Genomic Epidemiology of Meningococcal Disease.

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.

Meningococcal disease in the Middle East and Africa: Findings and updates from the Global Meningococcal Initiative.

The Global Meningococcal Initiative (GMI) has recently considered current issues in Middle Eastern and African countries, and produced two recommendations: (i) that vaccination of attendees should be considered for some types of mass-gathering events, as some countries mandate for the Hajj, and (ii) vaccination of people with human immunodeficiency virus should be used routinely, because of increased meningococcal disease (MD) risk. Differences exist between Middle Eastern and African countries regarding case and syndrome definitions, surveillance, and epidemiologic data gaps. Sentinel surveillance provides an overview of trends and prevalence of different capsular groups supporting vaccine selection and planning, whereas cost-effectiveness decisions require comprehensive disease burden data, ideally counting every case. Surveillance data showed importance of serogroup B MD in North Africa and serogroup W expansion in Turkey and South Africa. Success of MenAfriVac® in the African "meningitis belt" was reviewed; the GMI believes similar benefits may follow development of a low-cost meningococcal pentavalent vaccine, currently in phase 1 clinical trial, by 2022. The importance of carriage and herd protection for controlling invasive MD and the importance of advocacy and awareness campaigns were also highlighted.

Measuring Health Spillovers for Economic Evaluation: A Case Study in Meningitis.

The health of carers and others close to the patient will often be relevant to economic evaluation, but it is very rarely considered in practice. This may reflect a lack of understanding of how the spillover effect of illness can be appropriately quantified. In this study we used three different approaches to quantify health spillovers resulting from meningitis. We conducted a survey of 1218 family networks affected by meningitis and used regression modelling to estimate spillover effects. The findings show that meningitis had long-term effects on family members' health, particularly affecting the likelihood of family members reporting anxiety and depression. These effects extended beyond a single close family member. These findings suggest that vaccinating against meningitis will bring significant health benefits not just to those that might have contracted the illness but also to their family networks. In methodological terms, different approaches for quantifying health spillovers provided broadly consistent results. The choice of method will be influenced by the ease of collecting primary data from family members in intervention contexts. © 2015 The Authors. Health Economics published by John Wiley & Sons Ltd.

The health, social and educational needs of children who have survived meningitis and septicaemia: the parents' perspective.

BACKGROUND: Survivors of bacterial meningitis and septicaemia can experience a range of after-effects. There is little published research on the needs and provision of aftercare for children surviving bacterial meningitis and septicaemia. METHODS: Mixed methods study employing a survey and follow-up interviews with a sample of survey participants recruited from Meningitis Research Foundation's member database and social media. RESULTS: Of 194 eligible survey respondents, 77% reported at least moderate short-term after-effects, and 57% a need for aftercare or support. Most parents reported that their child received a hearing test (98%) and follow-up appointment with a paediatrician (66%). Psychosocial after-effects were most common and the greatest need was for educational support. About half of participants felt their children's needs for aftercare were met. We conducted interviews with 18 parents. Findings suggest access could be limited by: parents' inability to navigate systems in place, child's age, and delayed identification of sequelae. Parents felt a comprehensive explanation of possible after-effects on discharge from hospital was required, and found uncertain prognoses difficult. Good communication between professionals enabled a service tailored to the child's needs. CONCLUSIONS: Our study supports the NICE and SIGN guidelines and highlights areas for improvement in the aftercare of these children.

Counting the cost of meningococcal disease : scenarios of severe meningitis and septicemia.

BACKGROUND: Meningococcal disease can result in severe disabling sequelae, but there is no published information about the lifelong rehabilitation costs of patients with severe outcome in the UK. As cost-effectiveness studies play a crucial role in determining whether immunization programmes will be implemented, it is important to identify these costs. OBJECTIVE: The aim of the study was to estimate lifelong rehabilitation costs associated with severe cases of meningococcal disease and to present these costs in a format appropriate for use in a cost-effectiveness analysis. METHODS: Two severe scenarios of meningococcal disease with major sequelae were developed; one that presented acutely as meningitis and the other as septicemia. Scenarios were based on systematic reviews of the literature describing the sequelae of meningococcal disease, dialogue with Meningitis Research Foundation members who have experience of the disease, and discussions with pediatricians who have been responsible for managing children with this disease over many years. The two scenarios were devised to represent cases typical of the severe end of the spectrum. To obtain a comprehensive list of the health, educational and other resources used by survivors during and since their acute illness, families of individuals with sequelae similar to those in each of our scenarios were interviewed. Relevant academics and professionals in health, social care and education were consulted in order to ensure that our scenarios accurately represented the treatment and support that individuals with such sequelae might realistically receive from the National Health Service (NHS), the local authority and Personal Social Services (PSS). The majority of costs were derived from English Department of Health reference costs and unit costs of health and social care reflecting values for the financial year 2008-2009 indexed to 2010-2011. Costs were based on a life expectancy of 70 years in each scenario and are presented at a discount rate of 3.5 % for the first 30 years and 3 % thereafter, as recommended by the UK treasury (non-discounted costs are also presented for comparison). Costs are presented from both an NHS/PSS perspective and a government perspective. RESULTS: This study has revealed that severe cases of disease that result in long-term sequelae can result in costs to the NHS/PSS of around £160,000-£200,000 in the first year alone. Over a lifetime of 70 years, discounted costs from an NHS/PSS perspective ranged from approximately £590,000 to £1,090,000 (£1,250,000-£3,320,000 undiscounted) and discounted costs from a government perspective ranged from £1,360,000 to £1,720,000 (£3,030,000-£4,470,000 undiscounted). CONCLUSION: This study fills a gap in the UK literature and produces estimates that can be used in cost-effectiveness analysis to better represent the cost of illness at the severe end of the spectrum. Costs from a government perspective highlight the wider impacts of this disease, which is important for clinical decision makers, and budgetary and service planners to be aware of when making decisions about the benefits of implementing public health interventions such as immunization programmes.

Towards a meningitis free world--can we eliminate meningococcal meningitis?: contribution of the meningitis patient groups.

Patient groups play a critical part in the fight against meningitis in all its forms. The UK has the world's three largest meningitis patient groups, which over the past 3 decades have worked tirelessly in the fight against meningitis. Within the UK, where the patient groups work to prevent or alleviate the suffering caused by meningitis and septicaemia, their work is in three areas: continued research; demonstrating burden; and awareness-raising and advocacy. The research relates to developing and improving vaccines, and to improving outcomes for forms of meningitis that are not vaccine preventable. Demonstrating burden - showing the real impact of meningitis from a human perspective - highlights the need for vaccines to prevent the disease. Lives are saved by raising awareness of signs and symptoms and of the need for fast action, whilst advocacy can bring about change to improve the quality of life of those affected by meningitis. Awareness raising and advocacy also have the wider benefit of creating a climate in which people recognise the need for vaccines to prevent this dreadful disease. In addition, the patient groups seek to influence the early introduction and uptake of vaccines as they are licensed and approved by the expert bodies, the UK body being the Joint Committee for Vaccination and Immunisation (JCVI). Each area of activity is explored, and examples given from each of the patient groups of work they have done or are doing in that area.

What parents of children who have received emergency care think about deferring consent in randomised trials of emergency treatments: postal survey.

OBJECTIVE: To investigate parents' views about deferred consent to inform management of trial disclosure after a child's death. METHODS: A postal questionnaire survey was sent to members of the Meningitis Research Foundation UK charity, whose child had suffered from bacterial meningitis or meningococcal septicaemia within the previous 5 years. Main outcome measures were acceptability of deferred consent; timing of requesting consent; and the management of disclosure of the trial after a child's death. RESULTS: 220 families were sent questionnaires of whom 63 (29%) were bereaved. 68 families responded (31%), of whom 19 (28%) were bereaved. The majority (67%) was willing for their child to be involved in the trial without the trial being explained to them beforehand; 70% wanted to be informed about the trial as soon as their child's condition had stabilised. In the event of a child's death before the trial could be discussed the majority of bereaved parents (66% 12/18) anticipated wanting to be told about the trial at some time. This compared with 37% (18/49) of non-bereaved families (p = 0.06). Parents' free text responses indicated that the word 'trial' held strongly negative connotations. A few parents regarded gaps in the evidence base about emergency treatments as indicating staff lacked expertise to care for a critically ill child. Bereaved parents' free text responses indicated the importance of individualised management of disclosure about a trial following a child's death. DISCUSSION: Deferred consent is acceptable to the majority of respondents. Parents whose children had recovered differed in their views compared to bereaved parents. Most bereaved parents would want to be informed about the trial in the aftermath of a child's death, although a minority strongly opposed such disclosure. Distinction should be drawn between the views of bereaved and non-bereaved parents when considering the acceptability of different consent processes.

Early recognition of meningitis and septicaemia.

Meningitis is a disease feared by parents and health professionals alike. The rapid onset and progression of the disease and potentially lethal outcome makes it vital to diagnose the disease early, but this can be difficult. This is particularly the case during the current swine flu pandemic, where concerns have been raised that cases of meningitis may be missed due to a misdiagnosis of swine flu. Early symptoms of meningitis and septicaemia often resemble viral illnesses such as influenza, making the condition difficult to diagnose. Classic symptoms (the ones that many health professionals and lay people most commonly associate with meningitis), such as a nonblanching rash and a stiff neck, are often late symptoms of the disease and neck stiffness is rarer in infants and young children. The presence of ear or upper respiratory tract infections does not necessarily exclude a diagnosis of meningitis. The emphasis should therefore be on regular, close monitoring of an ill child and assessment of the vital signs. Awareness of the recognised "red flag" symptoms of septicaemia--cold hands and feet, limb pain and pale or mottled skin--could also aid earlier diagnosis and hence potentially improve prognosis.

Audiophile hardware in vision science; the soundcard as a digital to analog converter.

The design objective was to develop an inexpensive digital to analog (D/A) converter for use in vision science. Soundcards are hardware units that can be integral or can be added to a computer to add sound capability. A soundcard contains D/A converters designed to work in the audio frequency range, typically 20-20,000 Hz. Soundcard outputs are high-pass filtered and thus do not convey sub-audio frequency or dc information. It is possible to circumvent this design feature by programming the desired output waveform as an amplitude modulation of a high frequency carrier, and then demodulating the soundcard output. The circuit, using a 20 kHz carrier, provides precise D/A conversion for the frequency range relevant for vision experiments, dc to 100 Hz, using inexpensive readily available components. The specific application was for 8 channels of D/A conversion using a Macintosh computer running under OS X. The software needed to program stimuli was created using CoreAudio, a library for programming sounds in OS X. Using soundcards on other platforms would not be a problem, as long as there exists a low level library that would enable the wave table to be filled.