Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Understanding predictors of pneumococcal vaccine uptake in older adults aged 65 years and older in high-income countries across the globe: A scoping review

BackgroundPneumococcal disease causes substantial morbidity and mortality in older adults. Pneumococcal polysaccharide vaccine (PPV23) is routinely recommended to reduce the disease burden in this population. However, the vaccination coverage in older adults remains suboptimal in high-income countries.ObjectivesWe sought to understand the current landscape of published literature on the predictors of pneumococcal vaccine uptake in older adults aged 65 years and older in high-income countries, and to identify the gaps in literature to inform future research.MethodsWe conducted a scoping review employing the Arksey and O’Malley framework and Joanna Briggs Methods. We searched Medline, EMBASE, CINAHL, PsycInfo and Cochrane databases. We included quantitative and qualitative studies on predictors of pneumococcal vaccination in older adults that reported older adult- and pneumococcal vaccine-specific results, conducted in high-income settings, and published in English between January 2015 and April 2020. We excluded studies assessing interventions to improve vaccine uptake. We followed the Strategic Advisory Group of Experts on Immunization Working Group Vaccine Hesitancy Determinants Matrix to map the predictors within contextual, individual and social group, and vaccine and vaccination-specific influence determinants. Studies on providers and institutions were also included and results summarized separately.ResultsWe included 52 publications in our review. Most of the predictors in 39 quantitative studies belonged to the individual and social group influences (n = 12), followed by contextual influences (n = 11) and vaccine and vaccination-specific issues (n = 3). Few qualitative studies explored the barriers to pneumococcal vaccination. Only five studies examined predictors from the healthcare providers’ perspective. Three studies examined the institutional characteristics as the predictors of pneumococcal vaccination in older adults.ConclusionsWe identified enablers and barriers of pneumococcal vaccination among older adults in high-income settings. We also identified gaps in the literature and provide recommendations for future research to address the gaps.     

Burden of four vaccine preventable diseases in older adults

BackgroundImplementation of additional targeted vaccinations to prevent infectious diseases in the older adults is under discussion in different countries. When considering the added value of such preventive measures, insight into the current disease burden will assist in prioritization. The aim of this study was derive the first estimates of the disease burden in adults aged 50 years or over in the Netherlands for influenza, pertussis, pneumococcal disease and herpes zoster.MethodsThe average annual disease burden for these four diseases in the Netherlands was calculated for the period 2010–2013 using the disability-adjusted life years (DALY) measure. Disease models and parameters were obtained from previous research. Where possible we adapted these models specifically for older adults and applied age-specific parameters derived from literature. The disease burden based on these adapted models and parameters was compared with the disease burden based on the general population models.ResultsThe estimated average annual disease burden was from high to low: pneumococcal disease (37,223 DALYs/year), influenza (7941 DALYs/year), herpes zoster (942 DALYs/year), and pertussis (812 DALYs/year). The adaptation of models and parameters specifically for the elderly resulted in a higher disease burden compared to the use of general population models.ConclusionsAmong older adults, the disease burden in the period 2010–2013 was highest for pneumococcal disease, mostly because of high mortality, followed by influenza. Disease burden of herpes zoster and pertussis was relatively low and consisted mostly of years lived with disability. Better information on the course of infectious diseases and long-term consequences would enable more accurate estimation of disease burden in older adults.     

Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015–2016

Background

Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65?years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65?years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults.

Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines facilitates their uptake by older adults; however, data on immunogenicity and safety of concomitant administration of adjuvanted trivalent inactivated influenza vaccine (aIIV3) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) have not been reported.MethodsSubjects aged ≥65 years (N = 224) were randomized 1:1:1:1 to receive MF59-aIIV3 alone, MF59-aIIV3 + PPSV23 in contralateral arms, MF59-aIIV3 + PPSV23 in the same arm or PPSV23 alone (Clinical Trial Number – NCT02225327). Hemagglutination inhibition assay and multiplex opsonophagocytic killing assay were used to compare immunogenicity after single or concomitant vaccination.ResultsAll groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroconversion rates and geometric mean fold-increases, irrespective of concomitant vaccinations and injection site. For each pneumococcal serotype, opsonic index (OI) increased markedly after the PPSV23 vaccination, irrespective of the concomitant influenza vaccine. All subjects showed an OI ≥ 8 for serotypes 6B, 18C and 19A post-vaccination, with a suggestion that the ipsilateral concomitant vaccination might be associated with higher OIs for some antigens. Local and systemic adverse events were more common in subjects receiving PPSV23 compared to those receiving aIIV3 alone.ConclusionsNo interference was observed with antibody responses to influenza or pneumococcal antigens when aIIV3 and PPSV23 were administered concomitantly.     

Older adults' vaccine hesitancy: Psychosocial factors associated with influenza,pneumococcal, and shingles vaccine uptake

Influenza, pneumococcal disease, and shingles (herpes zoster) are more prevalent in older people. These illnesses are preventable via vaccination, but uptake is low and decreasing. Little research has focused on understanding the psychosocial reasons behind older adults’ hesitancy towards different vaccines. A cross-sectional survey with 372 UK-based adults aged 65–92 years (M = 70.5) assessed awareness and uptake of the influenza, pneumococcal, and shingles vaccines. Participants provided health and socio-demographic data and completed two scales measuring the psychosocial factors associated with vaccination behaviour. Self-reported daily functioning, cognitive difficulties, and social support were also assessed. Participants were additionally given the opportunity to provide free text responses outlining up to three main reasons for their vaccination decisions. We found that considerably more participants had received the influenza vaccine in the last 12 months (83.6%), relative to having ever received the pneumococcal (60.2%) and shingles vaccines (58.9%). Participants were more aware of their eligibility for the influenza vaccine, and were more likely to have been offered it. Multivariate logistic regression analyses showed that a lower sense of collective responsibility independently predicted lack of uptake of all three vaccines. Greater calculation of disease and vaccination risk, and preference for natural immunity, also predicted not getting the influenza vaccine. For both the pneumococcal and shingles vaccines, concerns about profiteering further predicted lack of uptake. Analysis of the qualitative responses highlighted that participants vaccinated to protect their own health and that of others. Our findings suggest that interventions targeted towards older adults would benefit from being vaccine-specific and that they should emphasise disease risks and vaccine benefits for the individual, as well as the benefits of vaccination for the wider community. These findings can help inform intervention development aimed at increasing vaccination uptake in future.     

Knowledge,attitudes and practices related to the influenza virus and vaccine among older adults in Eastern China

BackgroundThis study aims to assess the association between socio-demographic and health characteristics of older adults in Eastern China and knowledge, attitudes, and practices (KAP) about the influenza virus and vaccine.MethodsA prospective cohort of 1506 older adults (aged ≥60 years) was enrolled from November to December 2015 in Jiangsu Province. We examined the association between demographics, health and functional status, and cognitive impairment at enrollment with awareness of influenza virus and vaccine and KAP items focused on five Health Belief Model domains. At a 12-month follow-up interview we assessed change in awareness and readiness to be vaccinated.ResultsOne in five older adults was aware of the influenza virus (21%) or vaccine (20%); even fewer reported having at least “a little” knowledge of the virus and vaccine (7% and 4%, respectively); less than 1% reported ever receiving an influenza vaccine. Retirement, higher education and income, and normal cognitive status were consistently associated with both awareness and knowledge of influenza virus. The odds of having at least “a little” knowledge of the vaccine was 2.9-fold (95% CI = 1.6–5.3) higher among older adults with at least some secondary schooling. Among the 108 with knowledge of the virus, 55% said they “worry about getting the flu this season.” Among the 73 with knowledge of the vaccine, 92% believed the vaccine was at least somewhat effective and less than half (43%) thought that influenza vaccination was safe. At a 12-month follow-up interview, 33% (442/1333) increased from no knowledge to at least “a little”.ConclusionsIf and when influenza vaccines become widely available to older adults in China, our results indicate that influenza vaccination campaigns with basic information on the virus and vaccine could be beneficial for all older adults, especially those with less education and/or more cognitive impairment.     

A predictive model of the economic effects of an influenza vaccine adjuvant for the older adult (age 65 and over) population

Immunosenescence decreases influenza vaccine efficacy in older adults (age 65 and over). Strategies such as vaccine adjuvants are being developed to overcome immunosenescence. Our computer simulation model represented the decision to give an older adult either standard influenza vaccine or adjuvanted influenza vaccine and found the adjuvanted vaccine to be dominant in many scenarios, resulting in lowered cost and greater effectiveness. An adjuvanted vaccine that is 100% effective in overcoming immunosenescence remained dominant until its cost exceeded the standard vaccine cost by $65. In a single influenza season, the adjuvant would prevent 496,533 influenza cases, 171,981 hospitalizations, and 70,429 deaths.     

Attitude,knowledge and factors associated with influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency

BackgroundImmunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency.MethodsAn anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression.ResultsAmong the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57–60]) against seasonal influenza and 49% (95%CI [47–50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated.ConclusionDespite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections.     

Low vaccination coverage for seasonal influenza and pneumococcal disease among adults at-risk and health care workers in Ireland, 2013: The key role of GPs in recommending vaccination

The World Health Organization (WHO), and European Agencies recommend influenza vaccination for individuals at-risk due to age (≥65 years), underlying diseases, pregnancy and for health care workers (HCWs) in Europe. Pneumococcal vaccine is recommended for those at-risk of pneumococcal disease. In Ireland, vaccination uptake among at-risk adults is not routinely available. In 2013, we conducted a national survey among Irish residents ≥18 years of age, to estimate size and vaccination coverage of at-risk groups, and identify predictive factors for influenza vaccination.We used computer assisted telephone interviews to collect self-reported information on health, vaccination status, attitudes towards vaccination. We calculated prevalence and prevalence ratios (PR) using binomial regression.Overall, 1770 individuals participated. For influenza, among those aged 18–64 years, 22% (325/1485) [95%CI: 17%–20%] were at-risk; 28% [95%CI: 23%–33%] were vaccinated. Among those aged ≥65 years, 60% [95%CI: 54%–66%] were vaccinated. Influenza vaccine uptake among HCWs was 28% [95%CI: 21%–35%]. For pneumococcal disease, among those aged 18–64 years, 18% [95%CI: 16%–20%] were at-risk; 16% [95%CI: 12%–21%] reported ever-vaccination; among those aged ≥65 years, 36% [95%CI: 30%–42%] reported ever-vaccination. Main reasons for not receiving influenza vaccine were perceptions of not being at-risk, or not thinking of it; and among HCWs thinking that vaccination was not necessary or they were not at-risk. At-risk individuals were more likely to be vaccinated if their doctor had recommended it (PR 3.2; [95%CI: 2.4%-4.4%]) or they had access to free medical care or free vaccination services (PR 2.0; [95%CI: 1.5%-2.8%]).Vaccination coverage for both influenza and pneumococcal vaccines in at-risk individuals aged 18–64 years was very low. Influenza vaccination coverage among individuals ≥65 years was moderate. Influenza vaccination status was associated with GP vaccination recommendation and free access to vaccination services. Doctors should identify and recommend vaccination to at-risk patients to improve uptake.     

Estimating influenza vaccine effectiveness: Evolution of methods to better understand effects of confounding in older adults

Older adults are at high risk for serious complications of influenza illness and loss of vaccine-mediated protection. It is increasingly recognized that in addition to age, multiple chronic conditions and associated frailty contribute to the decline in vaccine effectiveness in this population. However, observational studies have been fraught with issues of confounding related to the degree of frailty and functional decline, measures of which are not included in standard administrative health care databases that are used to calculate vaccine effectiveness. This issue has led to the identification of confounding by indication or from “healthy vaccinee” bias, which respectively lead to underestimates or overestimates of influenza vaccine effectiveness. In addition, the sensitivity and specificity of the criteria used to define influenza-like illness declines with increasing age due to atypical presentations of illness and the inability to distinguish between influenza and other respiratory viruses. The test-negative case:control design has emerged as a method to estimate influenza vaccine effectiveness by comparing vaccination rates in those with laboratory-confirmed influenza to those with other acute viral respiratory illnesses. This review provides a perspective on how test-negative case:control study designs and new insights into mechanisms of protection have considerably strengthened influenza vaccination policy decisions for older adults that have historically been undermined by the conclusions of observational studies.     

Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan

To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n = 394) or to a non-PPV group (n = 392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P = 0.039) and for those who had difficulty walking (62.7%, P = 0.005), but not for all study subjects older than 65 years of age (P = 0.183), for the 2-year period. The Kaplan–Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P = 0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P = 0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age.     

The timing of influenza vaccination for older adults (65 years and older)

While studies have found influenza vaccination to be cost-effective in older adults (65 years or older), they have not looked at how the vaccine's economic value may vary with the timing of vaccine administration. We developed a set of computer simulation models to evaluate the economic impact of vaccinating older adults at different months. Our models delineated the costs and utility losses in delaying vaccination past October and suggest that policy makers and payors may consider structuring incentives (≤$2.50 per patient) to vaccinate in October. Our results also suggest that vaccination is still cost-effective through the end of February.     

Costs of vaccine delivery in the Gambia before and after,pentavalent and pneumococcal conjugate vaccine introductions

Background

The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV) in August 2009 and switched to 13-valent PCV in April 2011. In April 2009 monovalent hepatitis B and combined Diphtheria–Tetanus–Pertussis and Haemophilus influenzae type b vaccines were transitioned to a combined pentavalent vaccine. The current schedule offers three doses of PCV and pentavalent, and continues to give children monovalent hepatitis B vaccine at birth. We estimated the overall costs of the Gambian immunisation programme and the incremental costs of introducing pentavalent and the seven-valent PCV.

Methods

Twenty health facilities out of a total of 56 were surveyed. Data collected included number of vaccine doses delivered, staff time spent on vaccine delivery, distance travelled to collect vaccines, and cold chain expansion due to new vaccine introduction. National level data were collected from key informant interviews. Annualised costs were calculated in 2009 US$.

Results

With a PCV price of US$7 per dose, the incremental costs of introducing PCV was US$1.6 million, equivalent to US$25 per fully immunised child, with systems costs accounting for US$1.90. The switch to pentavalent vaccine resulted in cost savings of US$0.45 per fully immunised child. Total annual costs increased by 45% after the introduction of the new vaccines, amounting to US$ 3.0 million, or US$45 per fully immunised child.

Conclusion

Vaccine prices were the most important determinant of total incremental costs and cold chain expansion the biggest cost component of systems costs.     

Patterns and determinants of influenza and pneumococcal immunisation among adults with chronic disease living in Queensland, Australia

Using findings from a random, computer assisted telephone survey of households, this paper examines influenza and pneumococcal immunisation coverage and predictors of immunisation in 2203 adults with asthma, diabetes or a cardiovascular condition living in Queensland, Australia. 47% and 31% of high-risk persons were immunised against influenza and pnemococcus respectively. Immunisation coverage varied across chronic conditions and increased with age, being significantly higher for those aged 65 years and older and consequently eligible for free vaccination. Poor self reported health status was an independent predictor of pneumococcal vaccination status for people with asthma, diabetes or a cardiovascular condition; however it was only an independent predictor of influenza immunisation status for people with diabetes. Extending free vaccination to all people at risk may increase immunisation rates for younger people with a chronic condition     

Low uptake of nasal influenza vaccine in Polish and other ethnic minority children in Edinburgh,Scotland

Failure to vaccinate is well-recognised in Europe as a contributing factor to outbreaks of infectious diseases. Low immunisation rates are often associated with religious, social and ethnic minorities, including refugees or migrant groups. Polish people form Scotland’s newest and largest migrant group. They have moved to Scotland since 2004, joining established ethnic minorities from China, the Indian subcontinent and Africa.Scotland has had a seasonal influenza nasal vaccination programme for all primary school children since 2013. We investigated three primary schools in Edinburgh, which had reported low influenza vaccination uptake rates in 2016 and 2017 and found that these schools contained many pupils from ethnic minorities, the majority of whom were Polish. Pupils were categorized as one of three ethnic groupings: White British, Polish and Other Identified Ethnic Minority (OIEM). We ascertained ethnicity using NHS and Education Department information sources and name recognition. We examined vaccine acceptance, declination and non-return of consent forms.In 2017, nasal influenza vaccine uptake was 70.7% (65.2–75.6%, p?<?0.001) in White British, 60.9% (53.9–67.6%%, p?<?0.001) in other identified ethnic minorities and 25.0% (20.9–29.6%, p?>?0.001) in Polish children. White British children were more likely to return completed forms (78.9%) than other groups (OIEM 68.2% and Polish 61.8%). 36.8% of Polish families completed a consent form declining vaccination compared to 6.2% of White British families.These findings demonstrate that significant differences exist in nasal influenza vaccination uptake rates, which have important implications for the trans-national study of vaccine hesitancy. Further qualitative work and an investigation of uptake rates of other childhood immunisations in Polish and other migrant groups is required to assess differences in uptake and behaviours.     

Evaluation of impact of 23 valent pneumococcal polysaccharide vaccine following 7 valent pneumococcal conjugate vaccine in Australian Indigenous children

BackgroundHigh incidence and serotype diversity of invasive pneumococcal disease (IPD) in Indigenous children in remote Australia led to rapid introduction of 7-valent conjugate pneumococcal vaccine (7vPCV) at 2, 4 and 6 months in 2001, followed by 23-valent polysaccharide pneumococcal vaccine (23vPPV) in the second year of life. All other Australian children were offered 3 doses of 7vPCV without a booster from 2005. This study evaluated the impact of the unique pneumococcal vaccine schedule of 7vPCV followed by the 23vPPV booster among Indigenous Australian children.MethodsChanges in IPD incidence derived from population-based passive laboratory surveillance in Indigenous children <5 years eligible for 23vPPV were compared to non-Indigenous eligible for 7vPCV only from the pre-vaccine introduction period (Indigenous 1994–2000; non-Indigenous 2002–2004) to the post-vaccine period (2008–2010 in both groups) using incidence rate ratios (IRRs) stratified by age into serotype groupings of vaccine (7v and 13vPCV and 23vPPV) and non-vaccine types. Vaccine coverage was assessed from the Australian Childhood Immunisation Register.ResultsAt baseline, total IPD incidence per 100,000 was 216 (n = 230) in Indigenous versus 55 (n = 1993) in non-Indigenous children. In 2008–2010, IRRs for 7vPCV type IPD were 0.03 in both groups, but for 23v-non7v type IPD 1.2 (95% CI 0.8–1.8) in Indigenous versus 3.1 (95% CI 2.5–3.7) in non-Indigenous, difference driven primarily by serotype 19A IPD (IRR 0.6 in Indigenous versus 4.3 in non-Indigenous). For non-7vPCV type IPD overall, IRR was significantly higher in those age-eligible for 23vPPV booster compared to those younger, but in both age groups was lower than for non-Indigenous children.ConclusionThese ecologic data suggest a possible “serotype replacement sparing” effect of 23vPPV following 7vPCV priming, especially for serotype 19A with supportive evidence from other immunogenicity and carriage studies. Applicability post 10vPCV or 13v PCV priming in similar settings would depend on local serotype distribution of IPD.