Health promotion policies for elderly—Some comparisons across Germany,Italy, the Netherlands and Poland

ObjectiveThe aim of this study is to compare health promotion policies (HPP) for older adults in four European countries: Germany, Italy, the Netherlands and Poland. We focus on the design, regulations and implementation of policies in these countries.MethodAs policy relevant information is mostly available in national languages we have approached experts in each country. They filled in a specially designed questionnaire on the design, regulation and implementation of health promotion policies. To analyze the data collected via questionnaires, we use framework analyses. For each subject we define several themes.ResultsRegarding regulations, Poland and Italy have a top-down regulation system for health promotion policy. Germany and Netherlands have a mixed system of regulation. Regarding the scope of the policy, in all four countries both health promotion and prevention are included. Activities include promotion of a healthy life style and social inclusion measures. In Poland and Italy the implementation plans for policy measures are not clearly defined. Clear implementation plans and budgeting are available in Germany and the NetherlandsConclusionsIn all four countries there is no document that exclusively addresses health promotion policies for older adults. We also found that HPP for older adults appears to be gradually disappearing from the national agenda in all four countries.     

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness,research, and response

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders.     

A global agenda for older adult immunization in the COVID-19 era: A roadmap for action

Given our global interconnectedness, the COVID-19 pandemic highlights the urgency of building a global system that can support both routine and pandemic/epidemic adult immunization. As such, a framework to recommend vaccines and build robust platforms to deliver them to protect the rapidly expanding demographic of older adults is needed. Adult immunization as a strategy has the broad potential to preserve and improve medical, social, and economic outcomes, including maintaining functional ability that benefits older adults, their families, communities, and countries. While we will soon have multiple vaccines against COVID-19, we must recognize that we already have a variety of vaccines against other pathogens that can keep adults healthier. They can prevent simultaneous co-infection with COVID-19, and may favorably impact- the outcome of a COVID-19 illness. Further, administering a vaccine against COVID-19 requires planning now to determine delivery strategies impacting how older adults will be immunized in a timely manner. A group of international experts with various backgrounds from health and aging disciplines met to discuss the evidence case for adult immunization and crucial knowledge gaps that must be filled in order to implement effective policies and programs for older adult immunization. This group, coming together as the International Council on Adult Immunization (ICAI), outlined a high-level roadmap to catalyze action, provide policy guidance, and envision a global adult immunization platform that can be adapted by countries to fit their local contexts. Further meetings centered around the value of adult immunization, particularly in the context of COVID-19. There was agreement that programs to deliver existing influenza, pneumococcal, herpes zoster vaccines, and future COVID-19 vaccines to over a billion older adults who are at substantially higher risk of death and disability due to vaccine-preventable diseases are more urgent than ever before. Here we present a proposed framework for delivering routine and pandemic vaccines. We call upon the global community and governments to prioritize action for integrating robust adult immunization programs into the public health agenda.     

Importance of COVID-19 vaccine efficacy in older age groups

ImportanceAn effective vaccine against SARS-CoV-2 will reduce morbidity and mortality and allow substantial relaxation of physical distancing policies. However, the ability of a vaccine to prevent infection or disease depends critically on protecting older individuals, who are at highest risk of severe disease.ObjectiveWe quantitatively estimated the relative benefits of COVID-19 vaccines, in terms of preventing infection and death, with a particular focus on effectiveness in elderly people.DesignWe applied compartmental mathematical modelling to determine the relative effects of vaccines that block infection and onward transmission, and those that prevent severe disease. We assumed that vaccines showing high efficacy in adults would be deployed, and examined the effects of lower vaccine efficacy among the elderly population.Setting and participantsOur mathematical model was calibrated to simulate the course of an epidemic among the entire population of British Columbia, Canada. Within our model, the population was structured by age and levels of contact.Main outcome(s) and measure(s)We assessed the effectiveness of possible vaccines in terms of the predicted number of infections within the entire population, and deaths among people aged 65 years and over.Results In order to reduce the overall rate of infections in the population, high rates of deployment to all age groups will be critical. However, to substantially reduce mortality among people aged 65 years and over, a vaccine must directly protect a high proportion of people in that group.Conclusions and relevanceEffective vaccines deployed to a large fraction of the population are projected to substantially reduce infection in an otherwise susceptible population. However, even if transmission were blocked highly effectively by vaccination of children and younger adults, overall mortality would not be substantially reduced unless the vaccine is also directly protective in elderly people. We strongly recommend: (i) the inclusion of people aged 65 years and over in future trials of COVID-19 vaccine candidates; (ii) careful monitoring of vaccine efficacy in older age groups following vaccination.     

ESX-5-targeted export of ESAT-6 in BCG combines enhanced immunogenicity & efficacy against murine tuberculosis with low virulence and reduced persistence

Tuberculosis (TB) is the leading infectious cause of death globally. The only licensed TB vaccine, Bacille Calmette–Guérin (BCG), has low efficacy against TB in adults and is not recommended in people with impaired immunity. The incorporation of the Mycobacterium tuberculosis (Mtb) secretion system ESX-1 into BCG improves immunogenicity and protection against TB in animal models, which is associated with the secretion of the ESX-1-dependent protein ESAT-6. However, the resulting strain, BCG::ESX1^Mtb, has been deemed unsafe as a human vaccine, due to prolonged persistence and increased virulence in immunocompromised mice. In this study, we describe a new recombinant BCG strain that uncouples the beneficial aspects of ESAT-6 secretion from the detrimental ESX-1effects on virulence and persistence. The strain was constructed by fusing the ESAT-6-encoding gene esxA to the general secretion signal for the mycobacterial type VII secretion pathway protein PE25. This new strain, BCG::ESAT6-PE25SS, secretes full-length ESAT-6 via the ESX-5 secretion system, which in contrast to ESX-1 is also present in BCG. In vivo testing revealed that ESX-5-targeted ESAT-6 export, induces cytosolic contact, generates ESAT-6-specific T cells and enhances the protective efficacy against TB disease, but is associated with low virulence and reduced persistence in immunocompetent and immunocompromised mice. Additionally, compared to BCG::ESX1^Mtb and parental BCG, mucosal administration of BCG::ESAT6-PE25SS is associated with more rapid clearance from the lung. These results warrant further studies to evaluate BCG::ESAT6-PE25SS as a potential live attenuated vaccine candidate for TB.     

Factors affecting antibody responses to immunizations in infants born to women immunized against pertussis in pregnancy and unimmunized women: Individual-Participant Data Meta-analysis

BackgroundExploring factors that affect immune responses to immunizations in infants born to women immunized with tetanus-diphtheria-acellular-pertussis (Tdap) in pregnancy compared with unimmunized women is important in designing immunization programs.MethodsIndividual-participant data meta-analysis of 8 studies reporting post-immunization immunoglobulin G (IgG) levels to vaccine antigens in infants born to either women immunized with Tdap in pregnancy or unimmunized women, using mixed-effects models.ResultsIn infants of Tdap-immunized women, two-fold higher levels of anti-pertussis toxin (PT) and anti-diphtheria-toxoid (DT) IgG pre-primary immunization were associated with 9% and 10% lower post-primary immunization levels, (geometric mean ratio [GMR], PT: 0.91; 95% CI, 0.88–0.95,n = 494, DT: 0.9; 0.87–0.93,n = 519). Timing of immunization in pregnancy did not affect post-primary immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-primary immunization anti-B. pertussis and anti-DT levels. In infants of Tdap-immunized women, two-fold higher levels of anti-PT and anti-filamentous haemagglutinin (FHA) IgG pre-primary immunization were associated with lower post-booster immunization levels, (GMR, PT: 0.91; 0.85–0.97,n = 224, FHA: 0.92; 0.85–0.99,n = 232). Timing of immunization in pregnancy did not affect post-booster immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-booster immunization anti-PT, anti-pertactin (PRN), anti-TT and anti-DT IgG levels.In infants of unimmunized women, two-fold higher IgG levels of some vaccine antigens pre-primary immunization were associated with 8–17% lower post-primary immunization levels (GMR, PT 0.92, 95% CI:0.88–0.97, n = 373; FHA:0.88, 95% CI:0.85–0.92,n = 378; PRN:0.84, 95% CI:0.81–0.88, n = 367; TT:0.88, 95% CI:0.83–0.93, n = 241; DT: 0.83, 95% CI:0.79–0.87,n = 278). Two-fold higher levels of anti-FHA IgG pre-primary immunization were associated with 8% lower post-booster immunization levels (GMR, 0.92; 95% CI: 0.86–0.99,n = 138).DiscussionIncreased IgG levels pre-primary immunization is associated with reduced post-primary and post-booster immunization levels for some antigens in infants of women immunized or unimmunized in pregnancy, but their clinical significance is uncertain.     

Safety of measles and pertussis-containing vaccines in children with autism spectrum disorders

ObjectivesTo determine whether children aged 4–7 years with a diagnosis of autism spectrum disorders (ASD) were at increased risk of fever, febrile seizures, or emergency department (ED) visits following measles- or pertussis-containing vaccines compared with children without ASD.MethodsThe study included children born between 1995–2012, aged 4–7 years at vaccination, and members of six healthcare delivery systems within Vaccine Safety Datalink. We conducted self-controlled risk interval analyses comparing rates of outcomes in risk and control intervals within each group defined by ASD status, and then compared outcome rates between children with and without ASD, in risk and control intervals, by estimating difference-in-differences using logistic regressions.ResultsThe study included 14,947 children with ASD and 1,650,041 children without ASD. After measles- or pertussis-containing vaccination, there were no differences in association between children with and without ASD for fever (ratio of rate ratio for measles-containing vaccine = 1.07, 95% CI 0.58–1.96; for pertussis-containing vaccine = 1.16, 95% CI 0.63–2.15) or ED visits (ratio of rate ratio for measles-containing vaccine = 1.11, 95% CI 0.80–1.54; for pertussis-containing vaccine = 0.87, 95% CI 0.59–1.28). Febrile seizures were rare. Pertussis-containing vaccines were associated with small increased risk of febrile seizures in children without ASD.ConclusionChildren with ASD were not at increased risk for fever or ED visits compared with children without ASD following measles- or pertussis-containing vaccines. These results may provide further reassurance that these vaccines are safe for all children, including those with ASD.     

COVID-19 vaccination intention and activation among health care system employees: A mixed methods study

BackgroundAchieving high COVID-19 vaccination rates among employees is necessary to prevent outbreaks in health care settings. The goal of the study was to produce actionable and timely evidence about factors underlying the intention and decisions to obtain the COVID-19 vaccine by employees.MethodsThe study was conducted from December 2020 – May 2021 with employees from a VA health care system in Southeastern US. The study used a convergent mixed methods design comprising two main activities: a cross-sectional survey conducted prior to COVID-19 vaccine distribution, and semi-structured interviews conducted 4–6 months after vaccine distribution. Data were collected about participant characteristics, vaccination intention prior to distribution, vaccination decision post-distribution, determinants of vaccination intention and decision, activating factors, sources of information and intervention needs. Data from the survey and interviews were analyzed separately and integrated narratively in the discussion.ResultsPrior to vaccine distribution, 77% of employees wanted to be vaccinated. Post vaccine distribution, we identified 5 distinct decision-making groups: 1) vaccine believers who actively sought vaccination and included those sometimes described as “immunization advocates”, 2) go along to get along (GATGA) individuals who got vaccinated but did not actively seek it, 3) cautious acceptors who got the COVID-19 vaccine after some delay, 4) fence sitters who remained uncertain about getting vaccinated, and 5) vaccine refusers who actively rejected the COVID-19 vaccine. Participants identifying with Black or multiple races were more likely to express hesitancy in their vaccination intention.ConclusionThe findings of our study highlight distinct decision-making profiles associated with COVID-19 vaccination among employees of a VA health care system, and provide tailored recommendations to reduce vaccine hesitancy in this population.     

Estimating the number of US children susceptible to measles resulting from COVID-19-related vaccination coverage declines

Measles elimination hinges on vaccination coverage remaining above 95% to retain sufficient community protection. Recent declines in routine measles vaccinations due to the COVID-19 pandemic coupled with prior models indicating the country was close to the 92% herd immunity benchmark are a cause for concern. We evaluated population-level measles susceptibility in the US, including sensitivity analyses accounting for pandemic-related impacts on immunization. We estimated the number of children aged 0–18 currently susceptible to measles and modeled susceptibility proportions in decreased vaccination scenarios. Participants were respondents to the NIS-Teen survey between 2008 and 2017 that also had provider-verified vaccination documentation. The exposure of interest was vaccination with a measles-containing vaccine (MCV), and the age at which they were vaccinated for all doses given. Using age at vaccination, we estimated age-based probabilities of vaccination and modeled population levels of MCV immunization and immunity vs. susceptibility. Currently, 9,145,026 children (13.1%) are estimated to be susceptible to measles. With pandemic level vaccination rates, 15,165,221 children (21.7%) will be susceptible to measles if no attempt at catch-up is made, or 9,454,436 children (13.5%) if catch-up vaccinations mitigate the decline by 2–3%. Models based on increased vaccine hesitancy also show increased susceptibility at national levels, with a 10% increase in hesitancy nationally resulting in 14,925,481 children (21.37%) susceptible to measles, irrespective of pandemic vaccination levels. Current levels of measles immunity remain below herd immunity thresholds. If pandemic-era reductions in childhood immunization are not rectified, population-level immunity to measles is likely to decline further.     

Th1 memory: implications for vaccine development

Summary: T‐helper 1 (Th1) cells play a critical role, via interferon‐γ (IFN‐γ) production, in mediating intracellular killing against a variety of infectious pathogens. Thus, understanding the regulation of Th1 responses could provide better insight into vaccine design for infections requiring Th1 immunity. The cellular and molecular mechanisms that control the induction of Th1 effector cells have been well characterized. More recently, there has been substantial progress in furthering our understanding of the factors that regulate the development of Th1 memory cells. It is clear that Th1 responses are functionally heterogeneous, as defined by their ability to produce IFN‐γ. Furthermore, this heterogeneity has profound implications for the capacity of distinct lineages of Th1 cells to develop into memory cells. This review emphasizes the mechanisms controlling the differentiation of naïve CD4⁺ T cells into effector and then memory cells in a progressive manner. It highlights the importance of IFN‐γ as a positive regulator for inducing Th1 responses but a negative regulator for sustaining Th1 effector cells. In conclusion, we discuss how this current understanding of Th1 differentiation will inform vaccine design and better define immune correlates of protection.