ABSTRACT
The burden of seasonal influenza is particularly high in older adults. In 2017, 91% of the deaths from influenza disease and related complications in Australia were in adults ≥ 65 years of age.
Immunosenescence, an age-related decline in immune function, contributes to both an increased risk of developing influenza disease, and a poorer response to influenza vaccination, compared with younger adults. Furthermore, older persons are more likely to have severe disease and residual deficits in functional capacity after recovery.
Whilst vaccination is still regarded as the best method of protection, standard non-adjuvanted trivalent and quadrivalent influenza vaccines have suboptimal effectiveness in older adults, especially against the A/H3N2 strain. An MF59R-adjuvanted trivalent vaccine was introduced for use in adults ≥ 65 years of age in the 2018 influenza season, because this vaccine showed superior protection in older adults in clinical trials and real world studies.
Nurses are often in close contact with elderly patients, and play a critical role in seasonal influenza vaccinations and disease prevention in this age group. In this review, we discuss the burden of influenza disease in older adults, the vaccine options available for the 2019 influenza season, and how nurses can help encourage influenza vaccine uptake among older adults.
BURDEN OF INFLUENZA IN OLDER ADULTS
Influenza is a global disease, with epidemics occurring mainly in the winter in temperate areas, and throughout the year in tropical climates. Worldwide, seasonal epidemics cause three to five million severe cases and 300,000 to 650,000 deaths annually (WHO 2018).
In industrialised countries, deaths from influenza disease and related complications occur predominantly in older adults; in the 2017 influenza season in Australia, more than 91% of influenza-related mortalities occurred in people aged 65 years and over (Australian Government 2017).
Presentation of influenza symptoms can be different in older versus younger adults; older adults often have a lower incidence of fever, more frequent lower respiratory symptoms such as cough, wheezing, and chest pain, and atypical disease, with the only presenting symptoms being anorexia, mental status changes, or unexplained fever (Minnesota (USA) Department of Health 2018; Falsey et al. 2015).
Immunosenescence, an age-related decline in immune function, impairs the ability of older adults to fight natural infections, and also results in suboptimal immune responses to influenza vaccines (Haq and McElhaney, 2014).
This makes this age group particularly vulnerable to influenza disease and influenza-related complications, which are among the leading causes of mortality in older adults (US Government 2016).
In addition to mortality from influenza disease, the influenza season is also associated with higher rates of all-cause mortality from cardiovascular diseases, strokes, and pneumonia in the older adult population (Reichert et al. 2004).
Rates of hospitalisation from influenza disease are highest in young children and older adults; the non-pandemic 2006–2013 years in Australia saw an average of 30 hospitalisations per 100,000 population for adults aged 65–74 years, and 46 hospitalisations per 100,000 for adults aged ≥ 75 years (Fielding et al. 2013; Li-Kim-Moy et al. 2016). Hospitalisation is also associated with a loss of independence and diminished quality of life in older adults, even after discharge (Covinsky et al. 2003).
The estimated cost of influenza to the Australian healthcare system across all age groups is $115 million annually (Newall and Scuffham 2008). Because older adults have the highest burden of disease, the economic cost of influenza-related illness is expected to further increase as the population ages (Australian Bureau of Statistics 2013).
Vaccination is the best method available for preventing influenza disease, and annual seasonal influenza vaccination is recommended by the Australian Department of Health for all adults aged ≥ 65 years (Australian Government 2018).
Whilst prevention of influenza disease is the major aim of immunisation, minimising the consequences of disease and preserving the functional capacity of older persons is also important. Vaccination of older adults can also decrease the incidence of hospitalisations for pneumonia, and can reduce exacerbations in people with chronic obstructive pulmonary disease (Poole et al. 2006).
Influenza viruses change constantly due to small genetic mutations, a process called antigenic drift. Viruses circulating in one year are often not identical to those circulating in the previous year, hence the need for the strains included in seasonal influenza vaccines to be updated annually (Table 1). Individuals need to be vaccinated every year to provide the best level of protection, because the immune system may not recognise novel surface antigens expressed on the most current viral strains.
Table 1 – Australian Influenza Vaccine Committee recommendations on the composition of seasonal influenza virus vaccines for the 2019 season in Australia (AIVC 2019).
EGG-BASED QUADRIVALENT VACCINES
- A/Michigan/45/2015 (H1N1) pdm09-like virus
- A/Switzerland/8060/2017 (H3N2)-like virus
- B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage)
- B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage)
EGG-BASED TRIVALENT VACCINES
- A/Michigan/45/2015 (H1N1) pdm09-like virus
- A/Switzerland/8060/2017 (H3N2)-like virus
- B/Phuket/3073/2013-like (B/Yamagata/16/88 lineage)
A/H3N2 COMPONENT FOR NON-EGG-BASED VACCINES
- A/Singapore/INFIMH-16-0019/2016-like virus
WHAT HAPPENED DURING THE 2017 AND 2018 INFLUENZA SEASONS IN AUSTRALIA?
The 2017 influenza season in Australia was the most active since the 2009 pandemic (Australian Government 2017). The A/H3N2 strain was the most prevalent (55% of subtyped strains), and, consistent with previous seasons where A/H3N2 predominated, the ≥65 years age group were disproportionately affected. Hospitalisation rates from confirmed influenza disease were 2.3 times higher than the average of the previous five years, and over 91% of influenza-related deaths occurred in older adults (≥ 65 years old) (Australian Government 2017). The effectiveness of the 2017 vaccine was low overall (10–57% across strains), with lowest rates of vaccine effectiveness (VE) observed against the A/H3N2 strain (10%), thought in part to be caused by the genetic diversity in circulating A/H3N2 strains (Sullivan et al. 2017). In contrast to 2017, the 2018 season was less active. The A/H1N1 strain predominated (58% of subtyped strains) and accounted for the majority of hospital admissions.
As in 2017, the majority of influenza-related deaths were in older adults (≥80 years) (Australian Government 2017). Interim estimates of VE against GP visits and hospitalisation due to A/H1N1 were 77 and 83%, respectively, with a considerably higher VE overall than in the 2017 season, although estimates against the A/H3N2 strain were not calculable due to small sample sizes.
ADJUVANTED INFLUENZA VACCINE FOR USE IN ADULTS ≥ 65 YEARS OF AGE
Given the high burden of influenza disease in older adults during the 2017 season, the Australian Government’s Chief Medical Officer highlighted the severity of influenza disease and the importance of influenza vaccination for individual and communitywide protection (Australian Government 2018).
Because conventional (ie. non-adjuvanted or standard-dose) seasonal influenza vaccines are less effective in older adults (Goodwin et al. 2006) – in part due to immunosenescence, an adjuvanted trivalent influenza vaccine (aTIV; FluadR, Seqirus USA Inc., Summit, NJ, USA) and a high-dose TIV (Fluzone High-DoseR; Sanofi Pasteur Inc., Swiftwater, PA, USA; 180 μg antigen per dose) were made available for use in adults ≥65 years of age in Australia for the 2018 influenza season.
aTIV has recently been recommended as a priority for adults aged ≥75 years for the 2018–2019 season in the UK (UK Government 2018).
aTIV has demonstrated higher effectiveness than non-adjuvanted vaccines in older adults, particularly in reducing rates of influenza-related illness and hospitalisation (Domnich et al. 2017).
aTIV differs from non-adjuvanted trivalent influenza vaccines (TIVs) because it contains the adjuvant, MF59R (Novartis International AG, Basel, Switzerland), which enhances the immune response to vaccine antigens and promotes cross-reactive antibody responses (Ansaldi et al. 2010; Bihari et al. 2012; Khurana et al. 2011). aTIV (needle- and latex-free) contains the same quantity of A/H1N1, A/H3N2, and B strain antigens as are found in nonadjuvanted TIVs.
In a phase 3 clinical trial including 7,082 subjects ≥65 years of age, aTIV demonstrated higher immunogenicity, particularly against the A/H3N2 strain, a longer duration of enhanced immune response, and a greater degree of cross-reactivity against mismatched A/H3N2 strains, when compared with non-adjuvanted TIVs (Frey et al. 2014).
Because the vaccine antigen strain/clade may not be identical to the circulating viral strain/clade (termed mismatch), cross-reactive antibodies afford some level of protection against influenza infection when mismatch occurs.
In addition, aTIV has demonstrated an increased immune response in older adults with comorbidities, who have a higher risk of influenza-related complications (Frey et al. 2014).
Real world studies have also shown the VE of aTIV to be higher than that of standard-dose TIV in terms of laboratory-confirmed disease and reduced hospitalisations (Mannino et al. 2012; Van Buynder 2013).
In a recent study conducted to evaluate all-cause hospitalisation rates among elderly residents of nursing homes vaccinated with either aTIV or TIV, aTIV was shown to reduce the risk of hospitalisation during A/H3N2-dominant seasons (Gravenstein et al. 2018).
Residents from 412 (n = 26,300; 78% vaccination rate) and 410 (n = 26, 474; 79% vaccination rate) nursing homes received aTIV alone and TIV alone for the 2016–2017 influenza season, respectively.
Times to first hospitalisation were assessed from November 2016 to June 2017. Hospitalisations occurred in 20.8% of the residents in the aTIV-assigned nursing homes, and in 22.1% of residents in the TIV nursing homes (hazard ratio 0.94; confidence interval 0.88–0.99).
Because aTIV contains an adjuvant, a heightened immune response is generated initially at the injection site, which is associated with slightly higher rates of mild and transient injection site reactions (pain, erythema, and induration) compared with non-adjuvanted TIVs (Frey et al. 2014). To date, 107 million doses of aTIV have been distributed worldwide since first being approved in 1997; the vaccine is considered to be well tolerated with a good safety profile (O’Hagan et al. 2013).
HELPING TO INCREASE INFLUENZA VACCINE UPTAKE IN OLDER ADULTS
Improving influenza vaccination coverage is one of the priorities in the National Immunisation Strategy for Australia (Australian Government 2013). Despite the high influenza disease burden in older adults, the vaccination rate across Australia in people aged ≥65 years was estimated to be 74.8% since funding began in 1999, meaning that over a quarter of this age group remain unvaccinated (Dyda et al. 2016). A number of strategies have been shown to aid vaccine uptake in older adults, including proactively inviting patients for vaccination, educational outreach, and home visits (Table 2).
Table 2 – Strategies for increasing seasonal influenza vaccine uptake in older adults (Dexter et al. 2012; Newby et al. 2016; Thomas and Lorenzetti 2014)
- Have a lead member of staff who is responsible for the seasonal influenza program
- Use IT systems to identify eligible patients throughout the season
- Identify high-risk and high priority patients
- Proactively phone patients to invite them for vaccination
- Proactively ask patients if they have received their influenza vaccine yet
- Personally have a positive attitudes towards vaccination
- Opportunistically vaccinate patients
- Educate patients via posters, leaflets, and in-clinic information screens
- Provide information leaflets about influenza vaccination to patients collecting prescriptions
- Provide home visits for vaccine administration
- Host specific influenza vaccination clinics
Recommendation and advice about influenza vaccines from primary care professionals is one of the main factors associated with increased vaccine uptake in this age group (Dyda et al. 2016).
Many older adults are not aware of the potential seriousness of influenza disease, or are hesitant about receiving influenza vaccine (Horby et al. 2005). Often issues such as accessibility of clinics, unawareness of the need for vaccination, or the absence of reminders about the need for vaccination can be significant barriers to uptake (Nagata et al. 2013).
Nurses play a key role in overcoming vaccine hesitancy and educating patients about the benefits of seasonal influenza vaccination. Many patients are concerned about the effectiveness and safety of influenza vaccines, given the reports of poor VE in recent years. Poor VE may result from mismatch between the vaccine antigen strains/clades and circulating virus; however the MF59-adjuvanted vaccine may provide some cross-protection, depending on the degree of mismatch (Frey et al. 2014).
Patients may also be concerned about the misconception that vaccines can cause influenza disease. The vaccines available for use in older adults in Australia are all inactivated vaccines, and cannot cause influenza disease.
Whilst patients may experience flu-like symptoms such as muscle aches, headaches, and fatigue after receiving a vaccine, they can be reassured that these are just indicators of an immune response to the vaccine, rather than influenza disease.
Finally, because nurses are often the healthcare providers who work most closely with older adults, they are in an ideal position to give advice on additional lifestyle measures that can reduce the risk of influenza infection. Good overall health, including regular exercise, stressreduction, and good nutrition, can help prevent influenza disease or reduce the likelihood of complications.
Preventative measures such as frequent hand-washing, and avoiding contact with people who are sick can also help to reduce disease transmission (US Government 2018). In addition to these measures, and receiving the seasonal influenza vaccine every year, keeping up to date with other recommended vaccines (eg. pneumococcal vaccine for all adults ≥65 years old, and herpes zoster vaccine for all adults ≥70 years old) is beneficial to overall health and can help to reduce the risk of influenza-related complications, such as pneumonia.
CONCLUSION
Annual seasonal influenza vaccination is particularly important for older adults, who are at higher risk of morbidity and mortality from influenza disease and related complications. An adjuvanted TIV has been shown to be more effective than non-adjuvanted TIVs in older adults, and is available for use in adults ≥65 years of age for the 2019 influenza season in Australia. Nurses play a role of critical importance in increasing national rates of vaccination coverage, and are encouraged to be aware of and mindful of the availability and potential benefits of this adjuvanted vaccine for their older patients.
Acknowledgements
Author contributions: All authors made a significant intellectual contribution to the development of this paper, and approved the final draft of the manuscript for submission.
Conflicts of interest: MDC, AL, and PVB have no conflicts of interest to declare. The authors did not receive any form of payment from any source for writing this scientific report.
Funding statement: The preparation and publication of this manuscript were funded by Seqirus Vaccines Ltd.
The authors would like to thank Dr J Engelmoer (Sula Communications BV, Utrecht, The Netherlands) and Dr J Stirling (OLC Bioscience Ltd., London, UK) for editorial assistance in the preparation of this manuscript.
AUTHORS
Magali De Castro RN, BNursing, Dip (Mgt) is the Clinical Director at HotDoc Ltd., Melbourne, Victoria, Australia
Alan Leeb MBBCh, DTM&H, DCH, DFM, FRACGP is the Principal GP at llawarra Medical Centre, Ballajura, Western Australia, Australia
Paul Van Buynder MBBS, MPH, FAFPHM is Professor at Griffith University, School of Medicine, Southport, Queensland, Australia
