Nonstructural barriers to adult vaccination.

Adult vaccination coverage remains low, despite vaccine recommendations, improved access, and reimbursement. Low vaccination coverage and an aging population at higher risk from vaccine-preventable diseases lead to preventable disability and deaths, straining healthcare systems. An Advisory Board meeting was, therefore, held to identify non-structural barriers to adult vaccination and discuss potential solutions to increase uptake. Many non-structural factors can influence vaccine uptake, such as heterogeneity in the population, (fear of) vaccine shortages, incentives, or mandates for vaccination, understanding of disease burden and personal risks, time and opportunity for healthcare providers (HCPs) to discuss and deliver vaccines during general practice or hospital visits, trust in the health system, and education. To address these barriers, push-pull mechanisms are required: to pull patients in for vaccination and to push HCP performance on vaccination delivery. For patients, the focus should be on lifelong prevention and quality of life benefits: personal conversations are needed to increase confidence and knowledge about vaccination, and credible communication is required to build trust in health services and normalize vaccination. For providers, quality measurements are required to prioritize vaccination and ensure opportunities to check vaccination status, discuss and deliver vaccines are not missed. Financial and quality-based incentives may help increase uptake.

What is the context?● As populations age, healthcare systems are increasingly struggling with the burden of adult disease. Multiple vaccines are already recommended for adults throughout their lifetime, and more are coming soon, however, even in countries with subsidized programs, few adults are fully vaccinated, leading to frequent cases of illness, disability, hospitalization, or death, which could have been prevented.What is new?● Experts from Europe and the US joined an Advisory Board meeting to find out what is stopping people from getting vaccinated, particularly when vaccines are free, and how this can be helped in future.● The decision to get vaccinated can vary for different subgroups of the population, and can be influenced by vaccine shortages, rules about vaccination, and understanding the disease severity and need for vaccination. In addition, doctors may not have enough time and opportunity to discuss and provide vaccines during visits or may not feel comfortable raising the issue of vaccination with their patients.● To overcome these issues, both patients and doctors must change. Patients need: greater awareness of how illness impacts overall health and quality of life; better conversations with their doctors to address vaccination concerns; and trustworthy information from health services. For providers, vaccination prioritization should be linked to quality measurements, with collaboration from trusted community members to reinforce the importance of prevention, thus ensuring opportunities are not missed to discuss prevention and vaccinate. Normalizing adult vaccination is important for this.What is the impact?● Taking a patient centered prevention approach will help protect adults and ease the burden of vaccine-preventable disease.

Sustaining the momentum for adult vaccination post-COVID-19 to leverage the global uptake of life-course immunisation: A scoping review and call to action.

OBJECTIVES: The COVID-19 pandemic changed the adult vaccination landscape, possibly permanently. This review attempts to quantitate the magnitude of those changes. METHODS: PubMed was searched for studies on adult / life-course vaccination between 1 January 2020 until 8 November 2022. RESULTS: Twenty-one articles were identified and observations summarised as positive developments/impediments to life-course immunisation, and areas needing policy and structural reform. Unprecedented funding, international co-operation and technical advances led to COVID-19 vaccines authorised in record time. Investments in infrastructure and an expanded healthcare workforce streamlined vaccine delivery to adults. Constant media coverage and targeted messaging have improved health literacy. Conversely, the speed of vaccine development was perceived as a safety risk, and an 'infodemic' of misinformation propagated through social media negatively influenced vaccine uptake. Vaccine access and affordability remains inequitable among older adults and minority groups. CONCLUSIONS: The COVID pandemic led to an opportunity to permanently change policies, attitudes, and systems for vaccine delivery to adults to establish a global life-course approach to immunisation. This is a call for action to sustain the momentum triggered by the COVID-19 pandemic. Addressing inequalities, improving health literacy and optimally using social media are critical to sustain adult vaccinations in post-COVID-19 era.

Healthy ageing: Herpes zoster infection and the role of zoster vaccination.

Populations are ageing worldwide, with considerable time lived in ill-health, putting upwards pressure on healthcare budgets. Healthy ageing is defined as maintaining functional ability, including the ability to: meet basic needs; learn, grow and make decisions; be mobile; build and maintain relationships; and contribute to society. The risk and impact of infectious diseases increase with age due to immunosenescence. Vaccination can help to prevent disease in older adults, promoting healthy ageing and active lives. Herpes zoster (HZ) occurs when the varicella zoster virus is reactivated due to declining immunity. HZ is common, with a lifetime risk of one-third, and increases in incidence with age. HZ is associated with severe and intense pain, substantially affecting the functional status of patients as well as their overall health-related quality of life. HZ and its complications may result in prolonged morbidity, including persistent pain (post-herpetic neuralgia, PHN), hearing impairment, vision loss and increased risk of stroke and myocardial infarction. HZ and PHN are difficult to treat, substantiating the benefits of prevention. Vaccines to prevent HZ include a recombinant zoster vaccine (RZV). RZV has shown efficacy against the HZ burden of disease and HZ burden of interference on activities of daily living of over 90% in immunocompetent adults aged ≥50 years. Vaccine efficacy against HZ was maintained at over 70% at 10 years post-vaccination. Adult vaccination, including against HZ, has the potential to reduce burden of disease, thus helping to maintain functioning and quality of life to support healthy ageing in older adults.

Review of the unmet medical need for vaccination in adults with immunocompromising conditions: An Indian perspective.

Immunocompromised (IC) populations are at increased risk of vaccine-preventable diseases (VPDs). In India, the concern of VPDs in IC populations is particularly acute due to the prevalence of crowded living situations, poor sanitation and variable access to healthcare services. We present a narrative review of IC-related disease and economic burden, risk of VPDs and vaccination guidelines, based on global and India-specific literature (2000-2022). IC conditions considered were cancer, diabetes mellitus, chronic kidney disease, respiratory disorders, disorders treated with immunosuppressive therapy, and human immune deficiency virus (HIV). The burden of IC populations in India is comparable to the global population, except for cancer and HIV, which have lower prevalence compared with the global average. Regional and socioeconomic inequalities exist in IC prevalence; VPDs add to the burden of IC conditions, especially in lower income strata. Adult vaccination programs could improve health and reduce the economic impact of VPDs in IC populations.

What is the context?The population is aging, both globally and in India. Older age is associated with a weakened immune system. People with an immunocompromised (IC) status have a higher risk of contracting infections. The combination of these conditions greatly increases risk from infectious disease. A large percentage of infections, referred to as vaccine-preventable diseases (VPDs), could be avoided by vaccination. However, India-specific guidelines for adult immunization are limited and there is a low awareness of these recommendations among healthcare professionals and patients. What is new? The proportion of people with IC conditions in India is comparable to that seen in other countries. However, the risk of VPDs, such as influenza and bacterial pneumonia, is of particular concern in India; several factors, such as crowded living situation, poor hygienic conditions, and lack of access to healthcare may favor the spread of infections. The consequences of infections have the greatest impact on families with low income. Furthermore, only few India-specific guidelines exist with recommendations for adult immunization. What is the impact? There is a need to protect the growing IC populations against VPDs. The introduction of public healthcare and the experience from the nationwide COVID−19 immunization program in India provide an opportunity to extend adult vaccination programs covering other VPDs. Immunization programs could reduce the economic and disease burden associated with VPDs. Clear national guidelines and communication strategies are required to increase awareness of the benefit of vaccination.

Maintaining a 'fit' immune system: the role of vaccines.

INTRODUCTION: Conventionally, vaccines are thought to induce a specific immune response directed against a target pathogen. Long recognized but poorly understood nonspecific benefits of vaccination, such as reduced susceptibility to unrelated diseases or cancer, are now being investigated and may be due in part to "trained immunity'. AREAS COVERED: We discuss 'trained immunity' and whether vaccine-induced 'trained immunity' could be leveraged to prevent morbidity due to a broader range of causes. EXPERT OPINION: The prevention of infection i.e. maintaining homeostasis by preventing the primary infection and resulting secondary illnesses, is the pivotal strategy used to direct vaccine design and may have long-term, positive impacts on health at all ages. In the future, we anticipate that vaccine design will change to not only prevent the target infection (or related infections) but to generate positive modifications to the immune response that could prevent a wider range of infections and potentially reduce the impact of immunological changes associated with aging. Despite changing demographics, adult vaccination has not always been prioritized. However, the SARS-CoV-2 pandemic has demonstrated that adult vaccination can flourish given the right circumstances, demonstrating that harnessing the potential benefits of life-course vaccination is achievable for all.

Lifting non-pharmaceutical interventions following the COVID-19 pandemic - the quiet before the storm?

INTRODUCTION: In the first months of the novel coronavirus (COVID-19) pandemic that begun in 2020, non-pharmaceutical interventions (NPIs) have been adopted worldwide. However, the effects of NPI implementation go beyond slowing the spread of COVID-19. Here, we review the non-intended effects that may have arisen from prolonged application of NPIs. AREAS COVERED: NPIs also affected the epidemiology of other infectious diseases, with unprecedentedly low circulation of several respiratory and gastrointestinal viruses being observed worldwide in 2020. While this was a welcome effect for already strained health-care systems, prolonged low exposure to pathogens may result in an increased pool of individuals susceptible to certain diseases. Out-of-season or unusually intense outbreaks of non-vaccine preventable diseases have already been documented as NPIs were gradually eased. In the context of widespread and important disruptions in national vaccination programs during the early phase of the pandemic, the risk of vaccine-preventable disease resurgence after NPIs are lifted cannot be excluded either. EXPERT OPINION: Awareness must be raised of the risk of vaccine-preventable disease resurgence, and efforts need to be made to mitigate this risk, where possible, by increasing vaccination coverage. Research and regulatory opportunities brought on by the COVID-19 pandemic should be seized.

In the first months of the COVID-19 pandemic, the only methods available to slow the spread of the disease were non-pharmaceutical interventions, such as lockdowns, mask wearing, social distancing, school closures, and travel bans. Even after vaccines against COVID-19 became available, combinations of non-pharmaceutical interventions continued to be implemented by most countries, to various extents. Although these measures lowered the number of people who got sick before vaccines and therapies against COVID-19 were available, they also had other consequences for public health. The non-pharmaceutical interventions implemented worldwide have slowed or even stopped the spread of several infectious diseases: since 2020, fewer cases of flu, bronchiolitis, gastroenteritis, and other diseases were recorded compared to pre-pandemic times. This relatively long 2-year period during which people, especially children, were exposed to fewer infections might mean that their immune systems are less prepared to fight these diseases. In addition, vaccination against diseases other than COVID-19 dropped in the early months of the pandemic, meaning that the number of children and adults who are not protected against vaccine-preventable disease has potentially increased. Easing of COVID-19 restrictions has caused a comeback of some diseases against which no vaccine is available, sometimes with more cases than during the pre-pandemic years; there is a risk that this might happen with vaccine-preventable diseases as well. To prevent outbreaks, routine and catch-up vaccinations against other diseases besides COVID-19 should be encouraged and promoted.

Capturing the value of vaccination within health technology assessment and health economics: Literature review and novel conceptual framework.

BACKGROUND: Vaccination provides significant health gains to individuals and society and can potentially improve health equity, healthcare systems and national economies. Policy decisions, however, are rarely informed by comprehensive economic evaluations (EE) including vaccination's wide-ranging value. The objective of this analysis was to focus on health technology assessment systems to identify relevant value concepts in order to improve current EE of non-pandemic vaccines. METHODS: Following a literature review, a novel Value of Vaccination (VoV) framework was developed with experts in vaccine EE from developed countries with established health technology assessment systems. RESULTS: Forty-four studies presenting value frameworks or concepts applicable to vaccination were included. Eighteen unique value concepts relevant to EE were identified and defined. These were categorised within the VoV framework using three dimensions, moving from a narrow payer perspective to a more expansive and societal perspective. The dimensions were: (I) conventional payer perspective concepts (e.g., health gains in vaccinees, direct medical costs); (II) conventional societal perspective concepts (e.g., indirect health/economic gains to caregivers/households, productivity in vaccinees); and (III) novel societal concepts (e.g., financial risk protection, peace of mind, societal health gains, healthcare systems security, political stability, social equity and macroeconomic gains). While good quality evidence and methods are available to support concepts in Dimensions I and II, further work is needed to generate the required evidence for vaccination impact on Dimension III concepts. CONCLUSIONS: The devastating effect on nations of the COVID-19 pandemic has helped to highlight the potential far-reaching benefits that many vaccination programmes can offer. This VoV framework is particularly relevant to policy decisions considering EE, and the potential future expansion of non-pandemic vaccination value considerations. The framework helps to understand and compare current value considerations across countries and payer versus societal perspectives. It provides decision-makers with a transparent and logical path to broaden consideration of VoV in EE.

Unveiling the contributions of immunization for progressing towards Universal Health Coverage.

The aim of the United Nations' Sustainable Development Goal (SDG)3 is to ensure healthy lives and promote well-being for all, at all ages; including reducing maternal and child mortality, combating communicable and non-communicable diseases, and achieving Universal Health Coverage (UHC). UHC aims to provide everyone with equal access to quality essential and comprehensive healthcare services including preventions, interventions, and treatments, without exposing them to financial hardship. Making progress toward UHC requires significant investment in technical and financial resources and countries are pursuing the implementation of cost-saving measures within health systems to help them achieve UHC. Whilst many countries are far from attaining UHC, all countries, particularly low- and middle-income countries, can take steps toward achieving UHC. This paper discusses key data showing how immunization is a fundamental, cost-effective tool for reducing morbidity and mortality associated with infectious disease in all populations, creating more productive communities, reducing treatment costs, and consequently, facilitating social and economic advancement. Immunization is key to advancing toward UHC by relieving the burden that diseases place on the healthcare services, freeing essential resources to use elsewhere within the healthcare system. Immunization is an essential, readily available strategy that countries can deploy to achieve UHC and the SDG3 agenda.

Combining host-derived biomarkers with patient characteristics improves signature performance in predicting tuberculosis treatment outcomes.

Tuberculosis (TB) is a global health concern. Treatment is prolonged, and patients on anti-TB therapy (ATT) often experience treatment failure for various reasons. There is an urgent need to identify signatures for early detection of failure and initiation of a treatment switch.We investigated how gene biomarkers and/or basic patient characteristics could be used to define signatures for treatment outcomes in Indian adult pulmonary-TB patients treated with standard ATT. Using blood samples at baseline, a 12-gene signature combined with information on gender, previously-diagnosed TB, severe thinness, smoking and alcohol consumption was highly predictive of treatment failure at 6 months. Likewise a 4-protein biomarker signature combined with the same patient characteristics was almost as highly predictive of treatment failure. Combining biomarkers and basic patient characteristics may be useful for predicting and hence identification of treatment failure at an early stage of TB therapy.

Effect of vaccination on the use of antimicrobial agents: a systematic literature review.

BACKGROUND: Antimicrobial resistance is a growing global health threat. To preserve the effectiveness of antimicrobials, it is important to reduce demand for antimicrobials. OBJECTIVES: The objective of the study was to screen the existing peer-reviewed literature to identify articles that addressed the potential impact of influenza or Pneumococcus vaccination on antibiotic usage. Data sources: PubMed, Embase Study eligibility criteria: Clinical studies where antimicrobial prescribing was assessed in both vaccinated and unvaccinated populations. Participants and interventions: All patient populations were included (infants, children, adults and elderly), where the effects of the intervention (vaccination) was assessed. RESULTS: We identified unique 3638 publications, of which 26 were judged to be of sufficiently high quality to allow the calculation of the potential impact of vaccination. Of these studies 23/26 found a significant reduction in antibiotic use by at least one of the parameters assessed. LIMITATIONS: Different measures used to define anti-microbial use, studies typically focus on specific risk groups and most studies are from high-income countries. Conclusions and implications of key findings: Despite the limitations of the review, the evidence indicates that improved coverage with existing vaccines may significantly reduce antimicrobial demand. This suggests it may be a valuable tool for antimicrobial stewardship. Key messages While vaccines against a number of pathogens have been studied for their ability to reduce antimicrobial use, currently only vaccination against influenza or pneumococcus has generated sufficient data for analysis Vaccination against either influenza or pneumococcus significantly reduced overall antimicrobial prescribing rates, both in vaccinated individuals and at a population level Maintaining and expanding vaccination coverage thus appears to be a key tool for antimicrobial stewardship.

Identification of subclinical tuberculosis in household contacts using exposure scores and contact investigations.

BACKGROUND: The goal of tuberculosis elimination put forward in the End TB Strategy prioritizes diagnosis and treatment of incipient and subclinical TB, recently defined by key stakeholders as "asymptomatic, early pre-clinical disease during which pathology evolves". Regarded as indicative of a high risk of TB progression, considerable efforts have been made to identify these cases through exploration of biomarkers. The present study aimed to evaluate simple scoring systems for TB exposure as screening tools for subclinical TB, the only identifiable of the incipient and subclinical disease states, in a contact investigation (CI) setting of low HIV-prevalence. METHODS: Nested within a large prospective study in household contacts (HHCs) of smear positive pulmonary TB cases in South-India conducted 2010-2012, we assessed 1) the association between the Tuberculosis Contact Score (TCS) and the Infectivity Score, with established tools for Mycobacterium tuberculosis (Mtb) infection, corrected for established TB risk factors, and 2) the capability of the TB exposure scores to identify subclinical TB defined by Mtb-culture positivity in sputum or gastric aspirate (subjects < 5 years) specimen. RESULTS: Of 525 HHCs, 29 were Mtb-culture positive and 96.6% of these asymptomatic. The TCS and the Infectivity Score associated with positive Tuberculin Skin Test and QuantiFeron TB-Gold In-tube assay (QFT) results in multivariate analyses (TCS: ORTST 1.16, 95% CI: 1.01, 1.33; ORQFT 1.33 95% CI: 1.16, 1.51. Infectivity Score: ORTST 1.39, 95% CI: 1.10, 1.76; ORQFT 1.41 95% CI: 1.16, 1.71). The Infectivity Score showed a moderate capability to identify subclinical TB (AUC of 0.61, 95% CI: 0.52, 0.70). CONCLUSIONS: Although our results did not identify an easily applicable screening tool for subclinical TB, the present study indicates that focusing on TB-related symptoms in CI settings may be of limited value for early identification of HHCs with high risk for TB progression.

Precision Medicine and Vaccination of Older Adults: From Reactive to Proactive (A Mini-Review).

As populations age globally, the health of older adults is looming larger on the agendas of public health bodies. In particular, the priority is to ensure that older adults remain healthy, independent, and engaged in their communities. In other words, ensuring that increasing life spans are matched by increasing "health spans," meaning years spent in good health. Chronic conditions such as cancer or respiratory and cardiovascular diseases account for the bulk of the disease burden in older adults, and the consensus is that these can best be tackled by effective primary prevention. However, given the diverse nature of older populations, whose prior health experiences can be complicated by multi-morbidity and poly-pharmacy, effective primary prevention can be challenging. One approach that is gaining momentum is what is called "precision" or P4 medicine. The acronym stands for "predictive, personalized, preventive, participatory" medicine, and is based on the premise that preventing disease is better than treating it. However, effective prevention requires the ability to predict disease risk for a given patient, the tailoring of treatment to their circumstances, and their consent for or participation in the offered treatment. A P4 approach may seem counter-intuitive, given that vaccination is generally considered a public health intervention. However, in this article, we discuss the application of P4 medicine as a complement to planning the vaccination of older individuals, with a special focus on the important role that vaccine-preventable infections play in the burden of non-communicable disease.

Adult vaccination as part of a healthy lifestyle: moving from medical intervention to health promotion.

As the global population ages, there is concern about the effect of an increased proportion of older individuals on the economic sustainability of healthcare systems and the social effects of an older society. Health authorities and advocacy groups in countries at the forefront of this trend are now developing strategies to ameliorate the social and financial effects of an ageing population. There is broad agreement that for both society and for the individuals, it is important to ensure that increasing lifespans are matched with increased "healthspans" - the number of years spent in good health. There is also growing consensus that vaccination is one of the tools that can play an important role in improving adult health - though currently vaccination coverage is often poor. This review focuses on two issues that consistently appear to be associated with under-vaccination: the low awareness of risk (and potential consequences) for vaccine-preventable diseases and a poor understanding of the value of improved vaccination coverage for adults. We suggest that understanding of vaccination as a health-promoting activity, rather than a medical intervention designed to prevent the spread of a specific pathogen - is a crucial step to improve vaccination uptake among adults (see Supplementary video abstract ). Key messages As populations age globally, we are seeing an increasing burden of vaccine-preventable disease in adults. Adult vaccination against some common diseases has been shown to dramatically improve health and quality of life for older people. Despite the attested benefits, vaccination coverage is almost always poor in adults, even in countries where access is free at point of care. In this article, we discuss what appears to a neglected issue in adult vaccination, that of personal autonomy. We argue that adult vaccination will only be successful if it respects individual autonomy and that this requires treating the choice to vaccinate as a public health issue akin to smoking cessation, exercise and healthy diet.

Safety of AS03-adjuvanted influenza vaccines: A review of the evidence.

Clinical and post-licensure data have demonstrated that AS03-adjuvanted inactivated split virion vaccines, many with reduced antigen content, are effective against influenza infection. The objective of this review is to provide a comprehensive assessment of the safety of trivalent seasonal, monovalent pre-pandemic and pandemic AS03-adjuvanted influenza vaccines, based on non-clinical, clinical and post-licensure data in various populations. Non-clinical studies on local tolerance, toxicology and safety pharmacology did not raise any safety concerns with AS03 administered alone or combined with various influenza antigens. Data from clinical trials with over 55,000 vaccinated subjects showed that AS03-adjuvanted influenza vaccines were generally well tolerated and displayed an acceptable safety profile, although the power to detect rare events was limited. Approximately 90 million doses of A/H1N1pdm09 pandemic influenza vaccines (Pandemrix and Arepanrix H1N1) were administered worldwide, which contributed post-licensure data to the collective safety data for AS03-adjuvanted influenza vaccines. An association between Pandemrix and narcolepsy was observed during the A/H1N1pdm09 pandemic, for which a role of a CD4 T cell mimicry sequence in the haemagglutinin protein of A/H1N1pdm09 cannot be excluded. Provided that future AS03-adjuvanted influenza vaccines do not contain this putative mimicry sequence, this extensive safety experience supports the further development and use of AS03-adjuvanted inactivated split virion candidate vaccines against seasonal and pandemic influenza infections.

Would immunization be the same without cross-reactivity?

"Cross-reactivity" (the observed immune response against pathogen types not specifically targeted by the vaccine antigen composition) and "cross-protection" (clinical protection against related non-vaccine microorganism types) are vaccinology concepts that are attracting renewed interest in the context of disease prevention. National health authorities are collecting mounting evidence of the importance of cross-reactivity. For some vaccines, this has been substantiated by cross-protection data from clinical studies and/or post-licensure data, where their introduction into immunization programmes has shown beneficial impacts on disease caused by related non-vaccine microorganisms. This knowledge has influenced the way new vaccines are designed, developed, and evaluated in real-life settings. Some of the new vaccines are now designed with the specific aim of having a greater breadth of protection. Ideal vaccine antigens therefore include epitopes with conserved homology across related pathogen types, because it is not always possible to include the antigens of all the individual types of a given pathogen species. The use of novel adjuvants with greater immunostimulatory properties can also contribute to improved overall vaccine cross-reactivity, as could the use of antigen delivery platforms. The growing body of evidence allows us to better understand the full impact of vaccines - beyond vaccine-type disease - which should be taken into consideration when assessing the full value of vaccination programmes.

Incidence of tuberculosis and the influence of surveillance strategy on tuberculosis case-finding and all-cause mortality: a cluster randomised trial in Indian neonates vaccinated with BCG.

Introduction: Accurate tuberculosis (TB) incidence and optimal surveillance strategies are pertinent to TB vaccine trial design. Infants are a targeted population for new TB vaccines, but data from India, with the highest global burden of TB cases, is limited. Methods: In a population-based prospective trial conducted between November 2006 and July 2008, BCG-vaccinated neonates in South India were enrolled and cluster-randomised to active or passive surveillance. We assessed the influence of surveillance strategy on TB incidence, case-finding rates and all-cause mortality. Predefined criteria were used to diagnose TB. All deaths were evaluated using a verbal autopsy. Results: 4382 children contributed to 8164 person-years (py) of follow-up (loss to follow-up 6.9%); 749 children were admitted for TB evaluation (active surveillance: 641; passive surveillance: 108). The TB incidence was 159.2/100 000 py and the overall case-finding rate was 3.19 per 100 py (95% CI 0.82 to 18.1). Whereas, the case-finding rate for definite TB was similar using active or passive case finding, the case-finding rate for probable TB was 1.92/100 py (95% CI 0.83 to 3.78) with active surveillance, significantly higher than 0.3/100 py (95% CI 0.01 to 1.39, p=0.02) with passive surveillance. Compared to passive surveillance, children with active surveillance had decreased risk of dying (OR 0.68, 95%CI 0.47 to 0.98) which was mostly attributable to reduction of death from pneumonia/respiratory infections (OR 0.34, 95%CI 0.14 to 0.80). Conclusion: We provide reliable estimates of TB incidence in South Indian children <2 years of age. Active surveillance increased the case-finding rates for probable TB and was associated with reduced all-cause mortality.

Vaccination programs for older adults in an era of demographic change.

OBJECTIVES: Populations are aging worldwide. This paper summarizes some of the challenges and opportunities due to the increasing burden of infectious diseases in an aging population. RESULTS: Older adults typically suffer elevated morbidity from infectious disease, leading to increased demand for healthcare resources and higher healthcare costs. Preventive medicine, including vaccination can potentially play a major role in preserving the health and independence of older adults. However, this potential of widespread vaccination is rarely realized. Here, we give a brief overview of the problem, discuss concrete obstacles and the potential for expanded vaccination programs to promote healthy aging. CONCLUSION: The increasing healthcare burden of infectious diseases expected in aging populations could, to a large extent, be reduced by achieving higher vaccination coverage among older adults. Vaccination can thus contribute to healthy aging, alongside healthy diet and physical exercise. The available evidence indicates that dedicated programs can achieve substantial improvements in vaccination coverage among older adults, but more research is required to assess the generalizability of the results achieved by specific interventions (see Additional file 1).

A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31® in people living in a TB-endemic area.

BACKGROUND: H1/IC31® is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31® adjuvant. Previous trials have reported on the H1/IC31® vaccine in M. tuberculosis (Mtb)-naïve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31® was assessed in participants living in Ethiopia - a highly TB-endemic area. METHODS: Healthy male participants aged 18-25 years were recruited into four groups. Participants in group 1 (N = 12) and group 2 (N = 12) were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test (QFT) negative (Mtb-naïve groups), participants in group 3 (N = 3) were TST positive and QFT negative (BCG group), and participants in group 4 (N = 12) were both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1 formulated with the adjuvant IC31® (groups 2, 3 and 4) was administered intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were evaluated for up to 32 weeks after day 0. RESULTS: The H1/IC31®vaccine was safe and generally well tolerated. There was little difference among the four groups, with a tendency towards a higher incidence of adverse events in Mtb-infected compared to Mtb-naïve participants. Two serious adverse events were reported in the Mtb-infected group where a relationship to the vaccine could not be excluded. In both cases the participants recovered without sequelae within 72 h. Immunogenicity assays, evaluated in the 29 participants who received both vaccinations, showed a stronger response to TB antigens in the Mtb-naïve group vaccinated with the adjuvant. CONCLUSION: The trial confirmed the need for an adjuvant for the vaccine to be immunogenic and highlighted the importance of early phase testing of a novel TB vaccine candidate in TB-endemic areas. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on 14 January 2010.

Challenges in adult vaccination.

Life-long primary prevention interventions beginning and continuing throughout an individual's lifetime are increasingly seen as key to meeting the global healthcare challenges that accompany demographic changes - a concept referred to as "Healthy aging". In this perspective, vaccination is seen as part of a triad, together with healthy diet and exercise. Current adult vaccine coverage is lower than target vaccination rates in most developed countries, and so vaccine preventable diseases continue to present a substantial burden on health and healthcare resources, especially in older individuals. In part, this is due to lack of knowledge and understanding of the benefits of vaccination, inconsistent recommendations by providers and uncertainties about cost benefits. However, lower vaccine effectiveness in older adults plays a part, and new vaccines with novel characteristics to improve effectiveness in older adults are required. A life-course immunization approach to ensure optimal vaccine uptake across adults of all ages can be expected to reduce morbidity and mortality in later life. To achieve this, greater emphasis on public and healthcare provider education is necessary, based on appropriate economic analyses that demonstrate the overall value of vaccination. This article introduces the technical, economic, political and demographic issues that make establishing effective adult vaccination programs such a difficult, but pressing issue, and outlines some of the steps that are now being taken to address them. Key messages Life-long preventive activities that start and continue throughout life are essential, especially as the world's population is "getting older". This "Healthy aging" approach includes not only healthy diet and physical exercise; vaccination is critical in reducing some infectious diseases and their complications. Many adults, especially older adults (who have lower immunity than younger people) develop infections such as influenza and shingles that could potentially be prevented through vaccination. This review provides a perspective on the challenges in delivering a life-course immunization program. While some vaccines are less effective in older people, newer vaccines have been developed which provide stronger and longer protection in older patients than standard existing vaccines. However, the benefits of vaccination can only be realized if the vaccines are recommended and used. For that purpose, greater education of patients and their healthcare providers is necessary. Better knowledge of vaccines and making sure that all adults are up to date with all their recommended vaccines is an essential part of "Healthy aging". This should prevent not only vaccine-preventable diseases but also reduce the risk of complications in later life.