People who travel to countries where they are at risk of contracting specific infections often need specific vaccines. To make correct recommendations in this respect several points have to be considered. The state of health of the traveler should be known as well as his or her destination and travel style. Very important, however, is the age of the traveler. As advancing age leads to changes in the immune system, in older individuals many infections are more severe. On the other hand, most vaccines are less immunogenic in the elderly. In this chapter, we will discuss which vaccines are necessary for older travelers visiting (mainly) tropical and subtropical countries, how these vaccines have to be used, and if perhaps their use has to be altered in older individuals. First, standard vaccinations will be addressed. When the immunization state of the individual is incomplete because certain vaccinations are expired or missing, it has to be updated. Vaccinations against tetanus, diphtheria, influenza, pneumococcal diseases, measles, and poliomyelitis have to be considered in this respect, because the risk of getting infected with these diseases in tropical and subtropical regions or in regions with poor hygienic conditions is often higher or at least the same as in industrialized countries. The second and main part of this chapter contains the typical travel vaccines. We will deal with vaccinations against cholera, hepatitis A and B, Japanese encephalitis, invasive meningococcal diseases, rabies, typhoid fever, and yellow fever. Clinical courses and epidemiology of the different infections are presented. The respective vaccines are discussed in detail, especially their efficiency in older individuals as far as data are available in this respect. Finally, recommendations for their use in older travelers will be given. (c) 2020 S. Karger AG, Basel
Aging is associated with changes in the immune system. Both (innate and adaptive) arms of the immune system are involved. Natural killer (NK) cells are part of the innate immune system. They participate in host defense by eliminating cells that are virally infected, transformed, or senescent. They are also able to modulate the adaptive part of the immune system. As all cells, NK cells are subjected to changes with aging, which affects both their phenotype and functions. Aging is associated with various latent chronic viral infections, and the most significant among them is CMV. It is difficult to distinguish between the influence of CMV infection and that of aging itself on the NK cell properties. Recently, NK cells have been shown to be an important player in vaccine efficacy, which is also decreased with aging. In this chapter, we describe age-related changes in NK cells and their possible influence on the efficacy of vaccination in old age.
Older people have reduced immune responses to infection and vaccination. B cell activation is key for the efficacy of the vaccine response, but there are several age-related changes in B cells which may contribute to the loss of vaccine efficacy. Different subpopulations of B cells have different functions and phenotypes. These populations can change as we age; older people have been shown to have fewer "IgM memory" cells, regulatory B cells and plasma cells and more IgD-CD27- "double-negative" and "age-related B cells." While the overall quantity of antibody in the blood does not change, the quality of the B cell response changes; producing less specific antibodies upon challenge and more autoreactive antibodies. This could be due to changes in selection pressures, as has been demonstrated by repertoire sequencing of different subsets of B cells at different ages. Other changes in antibody repertoire are seen, including greater levels of IgG2 in older people and altered IgG1 IGHV gene usage. Since B cells rely on their environment for efficient responses, some of these changes may be due to age-related changes in accessory cells/signals. Other changes appear to be intrinsic to older/aged B cells themselves, such as their tendency to produce greater levels of inflammatory cytokines.
Immunization strategies for the elderly are frequently perceived as comprising only vaccines against influenza, Streptococcus pneumoniae, and herpes zoster. However, besides these vaccines, which are recommended specifically for the elderly, regular booster vaccinations against tetanus, diphtheria, and in some cases pertussis and polio, are recommended in many countries for adults including the elderly. Vaccination recommendations for adults differ greatly between individual countries and coverage data are scarce. A substantial proportion of adults, and particularly of the older age groups, do not have protective antibody concentrations against diphtheria, whereas tetanus-specific antibody concentrations are generally higher. Protection against pertussis is unsatisfactory in all adults, and development of improved vaccines is ongoing. Future vaccination strategies should include regular and well-documented booster shots throughout life, as post-booster antibody concentrations correlate with pre-booster antibody concentrations.
The following chapter is focused on the impact of comorbidities on the effectiveness of vaccination in older persons. Relevant comorbidities are cardiovascular diseases like hypertension, coronary artery disease or congestive heart failure, which lead to reduction of vaccine immunogenicity; or chronic obstructive pulmonary disease with a decline in lung function and a higher risk for pneumonia or infections due to influenza. End-stage renal disease has a high impact on developing infections and causes immune dysfunction over all parts of the immune system. Depression and dementia as well as psychological stress are associated with poor antibody response and a higher range of inflammation markers. Chronic inflammatory processes like rheumatoid arthritis also alter the immune system. In addition, geriatric syndromes and lowered functional status have implications for the vaccination response. Malnutrition is characterized by depletion of structural and functional proteins. This leads to a low antibody response. Negative immunomodulatory effects are also observed in vitamin D insufficiency. Frailty as well is associated with immunological changes and lowered performance in the activities of daily living, but moderate physical activity improves immune function.
Vaccine-preventable diseases represent a considerable burden on world health, and can have long-lasting consequences in those infected, especially in older adults, who can suffer functional decline, disability, and death. Vaccine uptake across the life course is desirable, but often suboptimal. A number of factors have been identified as contributors to low vaccine coverage, including sociodemographic characteristics, logistic factors such as ease of access and convenience, cultural attitudes including health literacy, and vaccine hesitancy. Strategies to improve vaccine uptake can target all the components underpinning low coverage, and include technology and communication-based strategies, physician-centered approaches, targeting healthcare workers for influenza vaccination, system-based factors, improved vaccine efficacy, and above all, political will and leadership.
The increase in the prevalence of obesity represents a worldwide phenomenon which is associated with several chronic diseases. In this review, we summarize published data showing how obesity, alone or together with the metabolic syndrome, induces defects in B cells similar to those induced by aging, contributes to systemic and B cell intrinsic inflammation and increases the secretion of autoimmune antibodies. We show that obese individuals contract more bacterial, viral, and fungal infections as compared to lean controls. These include periodontal, cutaneous, gastric, and respiratory tract infections, as well as postsurgical infections occurring after solid organ transplantation and surgeries for weight loss. Moreover, because obese individuals have a compromised immune system, they respond poorly to vaccination against influenza, hepatitis B, tetanus, and rabies. The results in this review highlight the importance to vaccinate individuals with obesity and/or with metabolic syndrome to prevent morbidity from vaccine-preventable diseases.
Vaccine development has traditionally been driven by the need to prevent high numbers of childhood deaths due to infectious disease. With few exceptions, vaccines for adults are the same as vaccines for infants, although it has long been apparent that they become less effective as age increases. It is only in the last few years that concerted efforts have commenced to develop life-long vaccination strategies through into older age. Impressive progress has been made in the field of vaccine technologies which, when they will be applied to vaccination of older adults, could change the landscape for disease prevention in this age group. The recently licensed adjuvanted herpes zoster vaccine shows that immunosenescence need not be a barrier to highly effective vaccination, and that highly effective vaccines for older adults can be achieved with good vaccine design. One of the greatest public health challenges of the 21st century is ensuring the health and well-being of the aged. New or improved vaccines targeting pathogens with a high disease burden in older adults have the potential to major contributions to the longevity and productivity of the older aged population.
Respiratory syncytial virus (RSV) causes infection throughout life, with infants, adults who are severely immunocompromised, and the elderly at special risk of developing lower respiratory tract disease, hospitalisation, and death. The burden of severe disease in the elderly is comparable to seasonal influenza, and there remains no effective anti-viral drugs or vaccine for any target population. The development of a vaccine to confer immunity against severe disease is a major global health priority. A multitude of safe and immunogenic vaccine candidates have failed to induce the protective immunity needed for licensure, and in recent years this has included the largest clinical trials of RSV vaccines in history. The obstacles to vaccine development in elderly populations include an incomplete understanding of the immune responses needed for protection, the effect of aging on induction and maintenance of immunity (natural and vaccine induced immunity), and the high rate of co-morbid disease in older adults. Recent advances in structural biology, new biological platforms for antigen delivery, and insights from experimental challenge models mark the latest developments in over 50 years of research. This continues to be an active and evolving field of scientific discovery with renewed hope for a vaccine in the future.
The collective loss of immune protection during aging leads to poor vaccine responses and an increased severity of infection for the elderly. Here, we review our current understanding of effects of aging on the cellular and molecular dysregulation of innate immune cells as well as the relevant tissue milieu which influences their functions. The innate immune system is composed of multiple cell types which provide distinct and essential roles in tissue surveillance and antigen presentation as well as early responses to infection or injury. Functional defects that arise during aging lead to a reduced dynamic range of responsiveness, altered cytokine dynamics, and impaired tissue repair. Heightened inflammation influences both the dysregulation of innate immune responses as well as surrounding tissue microenvironments which have a critical role in development of a functional immune response. In particular, age-related physical and inflammatory changes in the skin, lung, lymph nodes, and adipose tissue reflect disrupted architecture and spatial organization contributing to diminished immune responsiveness. Underlying mechanisms include altered transcriptional programming and dysregulation of critical innate immune signaling cascades. Further, we identify signaling functions of bioactive lipid mediators which address chronic inflammation and may contribute to the resolution of inflammation to improve innate immunity during aging.
Determining the optimal vaccination strategy for the protection of the elderly population against pneumococcal disease remains a challenge. Older adults are, second to young infants, most susceptible to become colonized and invaded by Streptococcus pneumoniae, causing serious disease such as bacteremic pneumonia, sepsis, and meningitis. In an era with increasing antimicrobial resistance and the growing susceptible population of aged adults, S. pneumoniae is a priority bacterial pathogen for research and development of new intervention strategies. While elderly indirectly profit from infant immunization programs through herd immunity, vaccination of older age groups can offer more direct protection. Two types of pneumococcal vaccines for adults, both based on capsular polysaccharide serotypes, are currently available but have limitations, such as short-lived protection or limited serotype coverage. These vaccine limitations and the biological aging of the immune system call for novel vaccination strategies for the older adults. Here, we highlight how host-pathogen interactions, immune protection, and effectiveness of currently available vaccines shift with increasing age, and how future pneumococcal vaccine strategies could be tailored for the elderly.
T lymphocytes follow three main stages of differentiation during their lifetime history - memory generation, memory homeostasis, and immunosenescence. Current definitions of T cell immunosenescence now include distinct aspects of both T cell senescence and exhaustion. Multiple studies have indicated a loss of vaccine efficacy in old age, and because this period coincides with the onset of T cell immunosenescence, the latter has often been implicated in the loss of vaccine responsiveness. This chapter examines changes in T cell homeostasis with age, and proposes mechanisms of how these changes, together with senescence and exhaustion, could affect the T cell contribution to the vaccine response. (c) 2020 S. Karger AG, Basel
Nosocomial infections represent a major global disease burden, and effective treatments are urgently needed, especially among older adult populations (≥65 years of age). With increasing age, risk factors for these infections increase due to underlying health conditions, immunosenescence, and increased contact with healthcare settings. In addition, many common nosocomial pathogens feature increasing rates of antibiotic resistance, compounding the problem and highlighting the need for prophylactic alternatives to antibiotic treatment, such as vaccines. In many cases, mortality rates associated with nosocomial pathogens that are antibiotic resistant are high. This chapter reviews the epidemiology of common nosocomial pathogens and diseases affecting older adult populations. Vaccines that are currently approved or in development for preventing disease caused by common nosocomial pathogens are also described. While important progress has been made in vaccine development for several pathogens such as Clostridium difficile and Staphylococcus aureus, there remains a crucial unmet need for vaccines to prevent the many common nosocomial infections, which disproportionately affect older adults.
Increased susceptibility to the serious complications of influenza is common in older adults. It is often ascribed to weakening of the immune system with age, and 90% of influenza-related deaths occur in older adults despite widespread vaccination programs. Common chronic conditions not only contribute to the loss of immune protection after vaccination and increase the risk for serious outcomes of influenza, but also increase the long-term consequences following hospitalization. Interactions of T and B cell ageing, chronic elevation of inflammatory cytokines (sometimes dubbed "inflammaging"), and dysregulated acute cytokine production pose major challenges to the development of new and more effective vaccines. However, these age-related problems are modifiable, as we have shown, and provide a clear margin for improvement. This chapter describes how an exclusive focus on developing influenza vaccines to stimulate strain-specific antibody responses against the hemagglutinin surface glycoprotein of the influenza virus, to the exclusion of other potentially important mechanisms, is missing the mark in terms of preventing the serious complications of influenza in older adults. Novel approaches are needed to enhance antibody-mediated protection against infection and stimulate cell-mediated immune responses to clear influenza virus from the lungs. These strategies for improving vaccine effectiveness will address the public health need for "vaccine prevention of disability" to mitigate the global pressures of aging populations on health and social care systems.
Herpes zoster (HZ; shingles) results from reactivation of varicella-zoster virus (VZV) after primary infection as varicella (chicken pox). It affects mainly older adults and people with immunocompromising diseases or treatments. The most common complication is postherpetic neuralgia (PHN), which has significant adverse effects on quality of life and activities of daily living. Since PHN cannot be prevented once HZ has occurred, and treatment is only modestly successful and is associated with significant side effects, the recent introduction of an effective vaccine is an important achievement. This new vaccine, which combines a single VZV glycoprotein (gE) and a multicomponent adjuvant, is superior to the previously available live attenuated VZV vaccine. The recombinant adjuvanted vaccine is remarkably effective in restoring the protective T cell-mediated immunity required to prevent HZ. Its clinical efficacy is much greater than that observed with other vaccines for older individuals affected by immune senescence, and its safety profile is very acceptable. It has been recommended in the USA and Canada for people who are 50 years of age and older. The immunogenicity and safety of this vaccine in severely immunocompromised individuals, such as after chemotherapy for malignancy, after solid organ or stem cell transplant, and in people with HIV are being studied.
Social networks of older adults with HIV have been characterized as fragile, with a greater reliance on friends as compared to family. However, we know little about the subgroup differences in the social network constellations of this population, how such characteristics are related to social support resources, and their relationship with psychosocial well-being. We developed a typology of social networks of older HIV-positive adults and examined if they would be related to receipt of informal assistance, perceptions of support sufficiency, and psychosocial well-being. Data were obtained from Research on Older Adults with HIV (n = 914). Participants were 50 years and older, HIV positive, and diverse in terms of race/ethnicity, gender, and sexual orientation. Cluster analysis identified Isolated, Friend-centered, and Integrated social network types. The Isolated reported significantly lower levels of assistance, lower perceptions of support availability and adequacy, greater stigma and psychological distress, and lower well-being compared to their peers. While friends dominate many social networks in this population, a more nuanced interpretation is needed; many have no friends and a substantial proportion receive significant family support. Those with Isolated network types will likely need to access a high volume of community-based services as they age as they lack informal support resources.
In this chapter, we will describe the state of the literature on behavioral health, which includes mental health and substance use problems, and the available treatment interventions to ameliorate these problems, for older adults living with HIV (OALH). The scientific literature on the behavioral health of OALH is highly underdeveloped, especially in terms of the creation of empirically supported interventions to alleviate psychological distress. From the literature that does exist, there are a number of salient factors that emerge, including stereotypes (i.e., older adults are not sexually active), stigmatization (of those who are HIV-positive), social isolation, unique psychosocial needs for newly-infected OALH, and elevated rates of emotional distress and concomitant disorders - especially, depression. These factors persist alongside findings that OALH have fewer sources of social or institutional support, fewer surviving peers, and a lack of family to care for them. Additionally, many OALH report problems with substance use, both as a function of their 'baby-boomer' generational status (i.e., people born between 1946 and 1964) and in terms of the life experiences associated with their HIV-positive status. Overall, it is unclear how mental health and substance use problems affect combination antiretroviral therapy adherence, multimorbidity, polypharmacy, or treatment outcomes in this population, and further study is needed.
The connection between palliative care and HIV infection has deep and wide roots in the United States that go back to the time when many gay men in the early 1980s were dying from a disease we knew little about, and there was no way to help but to alleviate symptoms in hospice and end of life centers across the United States. More individuals (adults and children), families, and communities attribute the success of antiretroviral therapies and other therapeutic approaches to advancing quality of life and life itself today. The identity of HIV, like many 'life-threatening illness with no cure' has evolved as a 'chronic' condition with a longer time period to address physical, social, and emotional experiences that may concern those living with HIV infection. Chronic conditions create an opportunity for healthcare providers from all types of disciplines to rethink and retool their knowledge and skills, to have conversations with those affected by HIV infection as to what they would ideally want in addressing their care needs; care needs that are now complicated by comorbid conditions of aging and healthcare reimbursement that uniquely intersect with HIV infection. This chapter addresses the current relevance of palliative care in HIV history, both nationally and internationally, and offers ideas for health professionals to use a multidisciplinary integration of knowledge to not just cure but align 'cure and care' toward healing action while being present to others from their perspective and values.
