Invasive meningococcal disease in older adults: current perspectives and call for action.

PURPOSE: Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60 years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. METHODS: An expert working group was established to evaluate clinical and epidemiological data to raise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. RESULTS: Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60 years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. CONCLUSIONS: IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations.

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Immunization technologies: Time to consider new preventative solutions for respiratory syncytial virus infections.

New technologies for the prevention of infectious diseases are emerging to address unmet medical needs, in particular, the use of long-acting monoclonal antibodies (mAb) to prevent Respiratory Syncytial Virus (RSV) lower respiratory tract disease in infants during their first RSV season. The lack of precedent for mAbs for broad population protection creates challenges in the assessment of upcoming prophylactic long-acting mAbs for RSV, with associated consequences in legislative and registration categorization, as well as in recommendation, funding, and implementation pathways. We suggest that the legislative and regulatory categorization of preventative solutions should be decided by the effect of the product in terms of its impact on the population and health-care systems rather than by the technology used or its mechanism of action. Immunization can be passive and active, both having the same objective of prevention of infectious diseases. Long-acting prophylactic mAbs work as passive immunization, as such, their recommendations for use should fall under the remit of National Immunization Technical Advisory Groups or other relevant recommending bodies for inclusion into National Immunization Programs. Current regulations, policy, and legislative frameworks need to evolve to embrace such innovative preventative technologies and acknowledge them as one of key immunization and public health tools.

Preventing Respiratory Syncytial Virus in Children in France: A Narrative Review of the Importance of a Reinforced Partnership Between Parents, Healthcare Professionals, and Public Health Authorities.

The highly contagious respiratory syncytial virus (RSV) is responsible for up to approximately 50,000 hospitalisations during each RSV season in children aged under 5 years in France, with the burden greatest in infants younger than 1 year who were born at term. There is a need for a strategy to universally protect young children from RSV infection, and thereby reduce the pressure that RSV places every year on RSV-infected children, their parents, and French healthcare systems. Potential strategies currently undergoing clinical investigation include passive immunisation via maternal vaccination or administration of long-acting monoclonal antibodies at or soon after birth, followed by vaccination later in infancy or childhood. An ongoing partnership and collaboration between parents, public health authorities, and frontline primary healthcare will need to be reinforced once these new RSV prevention strategies are available, to facilitate their use and ensure that all children receive adequate protection from the start of their first RSV season.

[Epidemiology and the burden of RSV]. / Épidémiologie et fardeau du VRS.

RSV is an almost obligatory virus responsible for upper (rhinitis and otitis) and lower (bronchiolitis and asthma attack) respiratory infections in children under 5 years of age. Reinfections are frequent at all ages because immunity is only partial and does not last long. Young children under the age of 1 are the most affected. The majority of these children are healthy. Having a risk factor (premature birth, heart disease, bronchopulmonary dysplasia, but also passive smoking) increases the severity of RSV pathology. Very few children currently benefit from prevention by anti-RSV monoclonal antibodies. The annual cost of care, the various socio-economic costs are a public health reality in three care sectors: out-patient, pediatric emergencies, hospitalization. Subsequent consequences: repeated wheezing and asthma, should also be taken into consideration and integrated into public health decisions. Progress in recognizing this pathology is desirable: distribution of diagnostic tests in the city; providing parents with information.

Le VRS est un virus quasi obligatoire responsable d'infections respiratoires hautes (rhinite et otite) et basses (bronchiolite et crise d'asthme) chez l'enfant de moins de 5 ans. Les réinfections sont fréquentes du fait d'une immunité partielle, peu durable, à tous les âges de la vie. Les jeunes enfants de moins de 1 an sont les plus touchés. La majorité de ces enfants sont bien portants. Avoir un facteur de risque (prématurité, cardiopathie, dysplasie bronchopulmonaire mais aussi tabagisme passif) majore la sévérité de la pathologie à VRS. Très peu d'enfants bénéficient actuellement d'une prévention par les anticorps monoclonaux anti-VRS. La charge annuelle en soins, les coûts socioéconomiques variés constituent une réalité de santé publique portant sur les trois secteurs de soins : ambulatoire, urgences pédiatriques, hospitalisation.Les conséquences ultérieures : répétition de wheezing, asthme, devraient aussi être pris en considération et intégrés dans les décisions de santé publique.Des progrès dans la reconnaissance de cette pathologie sont souhaitables : diffusion des tests diagnostiques en ville ; information aux parents.

Preventing invasive meningococcal disease in early infancy.

This review considers the pathogenesis, diagnosis, and epidemiology of invasive meningococcal disease in infants, to examine and critique meningococcal disease prevention in this population through vaccination. High rates of meningococcal disease and poor outcomes, particularly for very young infants, highlight the importance of meningococcal vaccination in early infancy. Although effective and safe meningococcal vaccines are available for use from 6 weeks of age, they are not recommended globally. Emerging real-world data from the increased incorporation of these vaccines within immunization programs inform recommendations regarding effectiveness, appropriate vaccination schedule, possible long-term safety effects, and persistence of antibody responses. Importantly, to protect infants from IMD, national vaccination recommendations should be consistent with available data regarding vaccine safety, effectiveness, and disease risk.

Care pathways in invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess in-hospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2.8 years (median). During hospitalization, 1,577 cases (44.6%) stayed in an intensive care unit, 1,238 (35.1%) required mechanical ventilation, and 43 (1.2%) underwent amputation; 293 cases (8.3%) died in hospital and a further 163 (4.6%) died following discharge; 823 cases (25.4% of survivors) presented ≥1 sequela and 298 (9.2%) presented multiple sequelae. The most frequently documented sequelae were epilepsy (N = 205; 5.8%), anxiety (N = 196; 5.5%), and severe neurological disorders (N = 193; 5.5%). All individual sequelae were significantly more frequent (p < .0001) in cases than controls. Hearing/visual impairment and communication problems were conditions that presented the highest risk for cases compared to controls (risk ratios >20 in all cases). In conclusion, this study highlights the importance of providing optimal medical care for patients with IMD, of minimizing the delay before hospitalization, and of effective prevention through comprehensive vaccination programs.

Benefits of providing optimal medical care for IMD patients.Importance of minimising the delay before hospitalization.IMD remains challenging to diagnose, and vaccination is the most efficient way to prevent the disease and its complications.

Healthcare Resource Consumption and Cost of Invasive Meningococcal Disease in France: A Study of the National Health Insurance Database.

INTRODUCTION: Invasive meningococcal disease (IMD) is an uncommon but serious infectious disease. Its economic burden is known to be high but is poorly characterised. The objective of this study was to determine costs, as captured in the healthcare claims database, incurred by all patients hospitalised for IMD in France over a 6-year period. METHODS: This case-control study was performed using the French national public health insurance database (SNDS). Cases comprised all individuals hospitalised with acute IMD in France between 2012 and 2017 inclusive. For each case, three controls were identified, matched for age, gender and region of residence. All healthcare resource consumption by cases and controls during the follow-up period was documented. Costs were analysed for the index hospitalisation in cases, 1 year following the index date and then for 5 years following the index date. Costs were assigned from national tariffs. The analysis was performed from a societal perspective. IMD sequelae were identified from hospital discharge summaries. RESULTS: A total of 3532 cases and 10,590 controls were evaluated. The mean per capita cost of the index IMD hospitalisation was €11,256, and increased with age and with the presence of sequelae. In the year following the index date, mean per capita direct medical costs were €6564 in cases and €2890 in controls. Annual costs were €4254 in cases without sequelae, €10,799 in cases with one sequela and €20,096 in cases with more than one sequela. In the fifth year of follow-up, mean per capita costs were €2646 in cases and €1478 in controls. The excess cost in cases was principally due to the management of sequelae. Amputation, skin scarring and mental retardation generated per capita costs in excess of €20,000 in the first year and in excess of €10,000 for subsequent years. CONCLUSION: The economic burden of IMD in France is high and, over the long-term, is driven by sequelae management.

Risk factors for invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Vaccination of at-risk populations against Neisseria meningitidis is an important strategy to prevent invasive meningococcal disease (IMD). The objective of this study was to characterize preexisting risk factors in patients with IMD and to compare their relative importance. This case-control analysis was performed in the French national public health insurance database (SNDS). Cases consisted of all people hospitalized for IMD in France over a six-year period (2012-2017). Controls were matched by age, gender, and district of residence. Medical risk factors were identified from ICD-10 codes in the SNDS. Socioeconomic risk factors studied were low household income and social deprivation of the municipality of residence. Associations of these risk factors with hospitalization for IMD were quantified as odds ratios (ORs) between cases and controls with their 95% confidence intervals (95%CI). The medical risk factors showing the most robust associations were congenital immunodeficiency (OR: 39.1 [95%CI: 5.1-299], acquired immunodeficiency (10.3 [4.5-24.0]) and asplenia/hyposplenia (6.7 [3.7-14.7]). In addition, certain chronic medical conditions, such as autoimmune disorders (5.4 [2.5-11.8]), hemophilia (4.7 [1.8-12.2]) and severe chronic respiratory disorders (4.3 [3.1-6.2]) were also strongly associated, as was low household income (1.68 [1.49-1.80]). In conclusion, this study has documented potential risk factors associated with hospitalization for IMD in a large and comprehensive sample of individuals with IMD in France. Several of the risk factors identified may help identify groups who could benefit from targeted prevention measures (such as vaccination) in order to reduce the burden of IMD.

Experts' opinion for improving global adolescent vaccination rates: a call to action.

Worldwide, lifestyle and resource disparities among adolescents contribute to unmet health needs, which have crucial present and future public health implications for both adolescents and broader communities. Risk of infection among adolescents is amplified by biological, behavioral, and environmental factors; however, infectious diseases to which adolescents are susceptible are often preventable with vaccines. Beyond these concerns, there is a lack of knowledge regarding adolescent vaccination and disease risk among parents and adolescents, which can contribute to low vaccine uptake. Promising efforts have been made to improve adolescent vaccination by programs with motivational drivers and comprehensive communication with the public. In May 2017, a multidisciplinary group of experts met in Amsterdam, Netherlands, to discuss adolescent vaccine uptake, as part of an educational initiative called the Advancing Adolescent Health Spring Forum. This article presents consensus opinions resulting from the meeting, which pertain to the burden of vaccine-preventable diseases among adolescents, reasons for low vaccine uptake, and common characteristics of successful strategies for improving adolescent vaccination.Conclusion: There is an urgent "call to action," particularly targeting healthcare providers and public health authorities, for the prioritization of adolescent vaccination as a necessary element of preventive healthcare in this age group.What is Known:• Despite increased risk of certain infectious diseases, adolescent vaccination uptake remains low.What is New:• Barriers to adolescent vaccine uptake include lack of information regarding vaccines and disease risk, health system inadequacies, and insufficient healthcare follow-up.• Successful efforts to improve adolescent vaccine uptake need cohesive leadership and involvement of multiple stakeholders, as well as youth-friendly messaging; healthcare providers and policymakers should prioritize adolescent vaccination and implement proven program strategies to improve adolescent health worldwide.

Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines.

Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedule was associated with a marked reduction in pertussis cases in the vaccinated cohort. However, due to the frequency of local and systemic adverse events after immunization with wPV, work on a less reactive vaccine was undertaken based on isolated B. pertussis components that induced protective immune responses with fewer local and systemic reactions. These component vaccines were termed acellular vaccines and contained one or more pertussis antigens, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), and fimbrial proteins 2 (FIM2) and 3 (FIM3). Preparations containing up to five components were developed, and several efficacy trials clearly demonstrated that the aPVs were able to confer comparable short-term protection than the most effective wPVs with fewer local and systemic reactions. There has been a resurgence of pertussis observed in recent years. This paper reports the results of a Consensus Conference organized by the World Association for Infectious Disease and Immunological Disorders (WAidid) on June 22, 2018, in Perugia, Italy, with the goal of evaluating the most important reasons for the pertussis resurgence and the role of different aPVs in this resurgence.

[Quadrivalent influenza vaccine: What is changed and what are the benefits?] / Vaccin grippal quadrivalent : quels changements pour quels bénéfices ?

Currently, circulating viruses responsible for annual seasonal influenza epidemics belong to two influenza A subtypes, A(H1N1) and A(H3N2), and to two antigenically distinct type B lineages, B/Yamagata and B/Victoria lineages. Like diseases due to influenza A virus, influenza B virus diseases may have severe consequences and should be prevented. Until now, in France, the vaccines used to prevent seasonal influenza were trivalent, systematically targeting viruses belonging to both A subtypes and to one or other of the B lineages. The protective efficacy of trivalent vaccines is diminished during the seasons when viruses belonging to both B lineages cocirculated or when the circulating dominant type B virus belonged to a lineage different from that targeted by the vaccine strain. By targeting viruses belonging to both B lineages, quadrivalent vaccines improve the antigenic concordance between circulating and vaccine type B strains. Three inactivated quadrivalent vaccines are authorized for marketing in France and should be available for the 2018-2019 season. It is expected that, by providing enlarged protection, these quadrivalent influenza vaccines will improve vaccine efficacy, the confidence in immunization of the public, the satisfaction of health professionals, and ultimately will help to complete immunization coverage.

Direct and Indirect Protection with Pediatric Quadrivalent Live-Attenuated Influenza Vaccination in Europe Estimated by a Dynamic Transmission Model.

Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2-17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7-17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366-3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2-17 years), QLAIV prevents 551-1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.

Population access to rotavirus vaccination in industrialized countries: lessons learnt from current experience.

BACKGROUND: Four steps are usually necessary before population access to vaccination programmes. Marketing authorization, appropriation by national agencies of the data, recommendation and policy-decision steps on funding and implementation. Using rotavirus vaccination as an illustrative case, this study aims at better understanding picture of population access, and identifying lessons learnt from current experience. METHODS: Systematic review of national vaccination policies in 20 countries. RESULTS: 12 countries have included rotavirus vaccination in their childhood national vaccination programme, two decided not to include it, decision is pending in three countries, while it has not started in the three remaining countries. Published evaluations and/or advice were available in 16 countries. Many differences in content and outcomes were identified. CONCLUSION: Rotavirus vaccination implementation across industrialized countries was disparate, leading to unequal population access over time. Comparative analyses of the decision-making process suggest different interpretations of available evidence, raising the need for a similar decision integrated framework, using a structured and systematic approach.

Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children. As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies.

Primary versus secondary failure after varicella vaccination: implications for interval between 2 doses.

BACKGROUND: Two-dose varicella vaccination is recommended for optimal control of varicella in populations with high (>90%) 1-dose coverage. Optimal timing of the second dose may depend on whether breakthrough varicella results from primary vaccine failure (no protective immunity after vaccination) or secondary vaccine failure (waning protective immunity). METHODS: Published literature (1995 to 2012) on vaccine failure after varicella vaccination cited in PubMed and other online sources was reviewed. RESULTS: Nineteen publications detailed 21 varicella outbreaks with breakthrough varicella rates ranging from 0% to 42%; the publications showed no consistent trend between breakthrough varicella rate and time since vaccination. CONCLUSIONS: Literature to date indicates a relatively high rate of primary vaccine failure and limited evidence of secondary vaccine failure among 1-dose varicella vaccine recipients, suggesting that a short interval between 2 doses might be preferable in countries considering implementation of universal varicella vaccination to reduce breakthrough varicella. However, any potential disruption to well-established vaccination schedules should be considered.