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Reinvigorating Influenza Prevention in US Adults Aged 65 Years and Older

Schaffner, William MD; Gravenstein, Stefan MD, MPH; Hopkins, Robert H. MD; Jernigan, Daniel B. MD, MPH

Infectious Diseases in Clinical Practice: November 2016 - Volume 24 - Issue 6 - p 303–309
doi: 10.1097/IPC.0000000000000462
NFID Clinical Updates

Adults aged 65 years and older are disproportionately impacted by influenza, accounting for more influenza-related deaths and hospitalizations than any other age group by far. The increasing likelihood of chronic conditions with age and age-related gradual decline in the immune system (immunosenescence) result in an elevated risk of complications from infections, including influenza. Immunosenescence is also a factor in reduced vaccine efficacy in older adults. Newer vaccines approved specifically for adults aged 65 years and older are designed to provide better immune response and better efficacy. Improving immunization coverage rates among this population using new and existing influenza vaccines is essential to reduce the annual impact of influenza infections in the United States.

From the *Vanderbilt University School of Medicine, Nashville, TN; †National Foundation for Infectious Diseases, Bethesda, MD; ‡Case Western Reserve University, Cleveland, OH; §University of Arkansas for Medical Sciences, Little Rock, AR; and ∥Centers for Disease Control and Prevention, Atlanta, GA.

Correspondence to: William Schaffner, MD, Vanderbilt University School of Medicine, Village at Vanderbilt, Suite 2600, 1500 21st Ave S, Nashville, TN 37212. E-mail:

The authors have no funding or conflicts of interest to disclose.

This publication is based on presentations by the authors and discussions among attendees during a National Foundation for Infectious Diseases (NFID) roundtable held in July 2016 in Bethesda, MD. This activity is supported by an unrestricted educational grant from Seqirus. The NFID also received funding and other support from Sanofi Pasteur. The policies of NFID restrict funders from controlling program content.


Physicians and other healthcare professionals interested in: seasonal influenza epidemics and the disproportionate effect they have on adults aged 65 years and older; newer vaccines available to help protect adults aged 65 years and older; and strategies to improve stagnating influenza vaccination rates in this vulnerable population.


After the educational activity, participants will be able to describe the impact of influenza on adults aged 65 years and older, discuss how immunosenescence affects influenza outcomes and response to vaccination, compare influenza vaccine options for adults aged 65 years and older in the United States, and identify best practices to overcome vaccination barriers.

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Overview: Protecting Adults Aged 65 Years and Older against Influenza

In the United States, adults aged 65 years and older are disproportionately impacted by influenza (flu) every year.1–4 There are far more influenza-related deaths and hospitalizations in adults aged 65 years and older than any other age group. Months after recovering from influenza symptoms, older adults may still be at an increased risk of a heart attack, stroke, or other cardiovascular problems.5 The increased risk is due to lingering inflammation and increased risk of thrombosis that may be associated with infections like influenza. In addition, even when all of these risks have passed, older adults may be left facing the reality that they will never fully regain their preinfluenza health and abilities, significantly impacting their lifestyle.6

Both the increasing likelihood of chronic conditions with age and the gradual decline in the immune system due to aging (immunosenescence) result in an elevated risk of complications from influenza and other infections for adults aged 65 years and older.7 Immunosenescence is also a factor in reduced vaccine efficacy in older adults. But age alone does not predict the severity of immunosenescence. Frailty, manifested as unintentional weight loss, self-reported exhaustion, weak grip strength, slow walking speed, and low physical activity,8 may more accurately predict the degree of immunosenescence and lowered response to vaccination than age alone.9,10

Despite the well-publicized risks that influenza poses for older adults, US influenza vaccination coverage has stalled in individuals aged 65 years and older during the last few seasons, and unfortunately dropped from 66.8% in the 2014-2015 season down to 63.4% in the 2015-2016 season.11 Influenza vaccine coverage rates are actually higher in infants aged 6 to 23 months (75%) and toddlers/preschoolers aged 2 to 4 years (69%), which is particularly notable because vaccination has been recommended for individuals aged 65 years and older since 1973 and for children only since 2004. There are many well-documented barriers to influenza vaccination,12–16 but one—the perception that influenza vaccination is not effective in older adults—is answered (at least in part) by newer vaccines formulated and approved specifically for those aged 65 years and older. Although influenza vaccines cannot prevent every case of influenza in older adults, vaccination reduces the risk of hospitalization, death, and long-term physical decline that older adults may experience if they get clinical influenza.17

The National Foundation for Infectious Diseases convened a roundtable to examine the impact of influenza in adults aged 65 years and older. Public health and medical experts along with health and consumer advocates examined the impact of influenza in individuals aged 65 years and older, discussed ways to improve vaccination rates in this vulnerable population, and considered the role of newer vaccines designed to provide better protection from the serious complications of influenza.

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Influenza in Older Adults and the Increased Risk of Heart Attack and Stroke

Influenza in older adults can have a somewhat different clinical presentation than what most think of as traditional influenza symptoms. The sudden onset of high fever typical in children and younger adults may be replaced by malaise in older adults.18,19 Sore throat, coryza, rhinitis, and nasal congestion are all less frequent in older adults, whereas gastrointestinal symptoms (pain, diarrhea, nausea, or vomiting) are more frequent.

Bacterial lung infection (bronchitis or pneumonia) is the most common complication of influenza, but influenza is more than a respiratory disease. Influenza and pneumonia can raise the risk of a first or subsequent heart attack by 3 to 5 times in the first weeks after infection and the risk remains elevated for several months (Table 1).5 Similarly, the risk of a first or subsequent stroke is increased 2 to 3 times in the first 2 weeks after infection and remains somewhat elevated for several months. The risk of heart attack and stroke remains elevated by approximately one third for as long as 3 months after influenza infection.5



Although influenza infection is positively correlated with the risk of heart attack and stroke, one study reported a negative correlation between influenza vaccination and the rate of first heart attack or stroke (Table 1).5 That is to say, when compared with unvaccinated individuals, those vaccinated had a lower risk of these outcomes in the months after vaccination.

Older individuals may experience both fewer systemic symptoms and localized respiratory symptoms based on their immune system response.18,19 Influenza infection can trigger a systemic inflammatory response that increases more slowly and lasts much longer in older adults compared with younger adults (often up to a week).20 Although short-term (acute) inflammation is a way for the body to fight infections and produces a prothrombotic state associated with vascular events, long-term (chronic) inflammation increases the risk of heart disease, cancer, and other serious illnesses.21

Finally, influenza infection is often associated with a significant negative impact on an older adult's ability to function independently. A study that included nearly 250,000 US nursing home residents showed a strong correlation between the severity of the circulating influenza strains and the amount of loss residents experienced in their ability to perform daily tasks such as dressing themselves, bathing, going to the bathroom alone, and eating meals without assistance.6 The level of functional decline measured in the study (a minimum of 4 points worsening in a validated measure of activities of daily living) can be reversed in less than 10% of long-term care residents, suggesting that the impact of influenza likely is permanent.

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Hospitalizations and Deaths From Influenza Increase with Age

The severity of influenza circulating in the community changes from year to year, but it is consistent that adults aged 65 years and older disproportionately experience the most serious outcomes.1–4 Annual variation in influenza severity affects the cumulative rates of laboratory-confirmed influenza hospitalizations in adults aged 65 years and older (Fig. 1), but a consistent and sharp increase in hospitalizations typically begins just before the end of the year, and continues for approximately 6 to 8 weeks before leveling off.2 In the severe 2014-2015 influenza season, there were more than 300 hospitalizations in the United States for every 100,000 adults aged 65 years and older.



Although there are far more influenza cases in younger persons, adults aged 65 years and older account for the majority of hospitalizations (Fig. 2).1 In the 2014-2015 season, in which a drifted H3N2 strain predominated and reduced vaccine effectiveness, 757,823 (78%) of the 974,206 hospitalizations estimated were in adults aged 65 years and older.22



United States surveillance systems do not track annual influenza-related deaths directly, except among children, but statistical methods estimate an influenza-related all-cause death rate of 133 per 100,000 people aged 65 years and older, more than 6 times the rate of 20 per 100,000 across all ages.4 These findings are consistent with estimates from other countries, where the mortality rates are 7 to 11 times higher in those aged 65 years and older than the general population.23–25

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The Burden of Influenza In the Aging Population

The first influenza virus subtype a person is exposed to may determine how they respond to different viruses later in life.26 Individuals currently aged 65 years and older were most likely first exposed to influenza A (H1N1), which was the predominant circulating influenza strain until 1947. In seasons where this strain predominates today, adults aged 65 years and older experience lower rates of hospitalization and death compared with seasons when influenza A (H3N2) is the more common virus.

Today's baby boomers, born between 1946 and 1964, may have less protection from influenza A (H1N1). Because it did not circulate as widely when they were young, they are less likely to have had their initial influenza exposure to this virus group. As baby boomers age into the 65-plus population, they may be more susceptible to influenza A (H1N1) strains. This may result in a higher burden of disease as this generational group ages.

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Improving Influenza Vaccines for Older Adults

A variety of strategies have been explored for developing influenza vaccines that are able to overcome age-related immunosenescence.27 Two of these strategies have received US Food and Drug Administration (FDA) approval for use in the United States in adults aged 65 years and older.

Fluad, an adjuvanted influenza vaccine for adults aged 65 years and older, was first made available in the United States for the 2016-2017 season. Meanwhile, the vaccine has been in use in Italy since the 1990s and is licensed for use in 38 other countries including Canada and 15 countries in Europe.28 Vaccine safety has been confirmed in clinical and observational studies including approximately 120,000 subjects and more than 60 million doses had been administered to older adults worldwide by 2013.29 This vaccine is associated with more injection site reactions compared with standard-dose vaccine.

In a randomized, observer-blinded, multicenter, clinical trial of 7104 adults aged 65 years and older (mean age, 72 years), adjuvanted influenza vaccine elicited a higher antibody response than standard-dose vaccine for all 3 influenza strains (A/H1N1, A/H3N2, B), and for both homologous and heterologous A strains.30 However, preestablished superiority criteria by the FDA were met only for influenza A (H3N2), the strain causing the most severe disease across all age groups.

There are no prospective, randomized efficacy trials reported, but a number of observational studies have reported on the effectiveness of adjuvanted influenza vaccine in older adults. In a large cohort study (170,988 person-seasons of observation) conducted in Italy during 3 seasons, the risk of hospitalization from influenza or pneumonia was 25% lower in patients who received adjuvanted vaccine compared with standard vaccine.31 In a Canadian case-control study (N = 282), adjuvanted vaccine was superior to standard vaccine in preventing influenza infection in nursing home patients.32 An Italian prospective cohort study of 3173 nursing home residents with a mean age of 85 years reported protection rates of 80% for adjuvanted vaccine versus 57% for standard vaccine.33

Fluzone High-Dose (influenza virus vaccine, inactivated), which contains 4 times more antigen than standard-dose vaccine (60 μg hemagglutinin of each influenza strain per 0.5 mL dose vs. 15 μg for standard dose), was approved in the United States in 2009 and has been recommended for those aged 65 years and older since first becoming available for the 2010-2011 season. Since introduction, more than 50 million doses have been distributed in the United States, and, during the 2015-2016 season, approximately 50% of US seniors who received any influenza vaccine received high-dose vaccine (Data on file, Sanofi Pasteur). Vaccine safety has been established in pre- and many postlicensure studies as well as in clinical use. The vaccine is associated with more injection site reactions compared with standard-dose vaccine.

In a randomized, double-blind, multicenter clinical trial of 3876 adults aged 65 years and older (mean age, 73 years), high-dose vaccine elicited significantly higher antibody responses compared with standard-dose vaccine for all 3 influenza strains (A/H1N1, A/H3N3, B).34 The high-dose vaccine met superiority criteria for both A strains.

Since the introduction of the high-dose vaccine, 5 publications have reported on a postlicensure efficacy trial.35–39 A 2-season randomized, double-blind trial of nearly 32,000 adults aged 65 years and older reported that recipients of the high-dose vaccine had a 24.2% lower risk of symptomatic laboratory-confirmed influenza compared with recipients of standard-dose vaccine, and the high-dose vaccine met prespecified FDA superiority criteria.35 This trial also showed that high-dose vaccine was associated with a 7% relative reduction in all-cause hospitalizations, an 18% relative reduction in cardiorespiratory events potentially related to influenza, and a 40% relative reduction in pneumonia.37

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Influenza Vaccine Options for Adults Aged 65 Years and Older

The Centers for Disease Control and Prevention (CDC) recommends annual influenza vaccination for all eligible individuals aged 6 months and older, optimally before the onset of influenza activity in the community, but vaccination should continue for as long as influenza continues to circulate, without a preferential recommendation for a specific influenza vaccine.40 Individuals aged 65 years and older will now have multiple vaccine options available, including high-dose and adjuvanted vaccines, in addition to standard-dose 3- and 4-strain vaccines (trivalent and quadrivalent vaccines).

Influenza vaccine effectiveness varies seasonally based on the match between circulating and vaccine strains and the specific measures of effectiveness that are studied.41 Vaccine effectiveness measures may range from prevention of influenza infection to prevention of death, with many outcome measures in between—each of which will result in a unique estimate of effectiveness. Regardless of the measure studied, effectiveness of the standard-dose vaccine tends to decrease with increasing age. However, CDC and the medical community agree that vaccination with any available influenza vaccine, including standard dose, is better than not vaccinating, regardless of the patient's age.

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Challenges to Protecting Adults Aged 65 Years and Older from Influenza

Certain barriers to influenza vaccination may be more relevant for adults aged 65 years and older compared with younger adults. Older adults are more likely to have chronic diseases and—because these patients worry about managing their underlying medical conditions—they may overlook an annual influenza vaccine. Although primary care health care professionals (HCPs) are more likely to vaccinate in their offices, patients with chronic diseases may see specialists more often than primary care HCPs. For this reason, it is imperative that all HCPs, specialists and nonspecialists alike, make a strong influenza vaccine recommendation to every patient during influenza season to minimize missed opportunities.

Although the universal recommendation for all adults to receive an annual influenza vaccination seems simple, there are several vaccines approved for adults aged 65 years and older. Patients may be confused about which vaccine to get or they may have a preference for a vaccine that is not available in the location they access for vaccination. In all cases, vaccination should be the primary goal—older adults may receive the high-dose or adjuvanted vaccine if it is available, but should not forego vaccination in any case.

Finally, there may be cost considerations. Medicare provides full coverage for influenza vaccines, regardless of which influenza vaccine a patient receives. For HCPs, however, the cost to purchase different types of vaccine may vary and may influence how much and which vaccine(s) they stock. This may make it difficult, particularly for large systems, nursing homes, and community immunizers to stock every type of vaccine and provide the optimal protection for older adults.

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Best Practices for Influenza Prevention in Adults Aged 65 Years and Older

In the United States, the one third of individuals aged 65 years and older who forego annual influenza vaccination illustrates the ongoing need for education and awareness among the public and among HCPs who care for this population. Improving influenza vaccination coverage requires ongoing annual collaborative efforts among public health officials, advocacy groups, professional societies, and other vaccine stakeholders including HCPs and the public. All stakeholders should support and encourage efforts to include influenza vaccination in quality and performance measures, both on the local and national levels.

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Be Prepared to Answer Patient Questions (Whether or Not Vaccines are Provided)

Although universal influenza vaccination recommendations are simple on the surface (annual vaccination for all), questions persist from HCPs, patients, families, and health system administrators, among others. The HCPs should be well educated about influenza vaccine options and armed with simple and quick answers to frequently asked questions (see Frequently Asked Questions About Influenza Vaccination for Adults Aged 65 Years and Older in next section). It is important for HCPs, in both primary care and specialty practices, to understand the benefits of influenza vaccines that are licensed in the United States specifically for adults aged 65 years and older. A strong HCP recommendation is important, even in practices that do not offer vaccines, because it is significantly associated with consumer vaccination uptake.12,15,42

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“Walk the Walk” by Making Sure You and Your Staff Are Vaccinated Annually Against Influenza (and Up-to-Date on All Other Recommended Vaccines)

The HCPs need to set a good example for their patients. It is also their responsibility to protect patient safety by making sure everyone who cares for, or comes in contact with patients, has been vaccinated. In addition, the practice with a fully vaccinated staff is less likely to experience absenteeism or presenteeism— employees coming to work sick and performing suboptimally during winter respiratory season when patients need them. Practice leaders need to make their vaccine commitment known to every staff member—both clinical and administrative—so that everyone echoes this commitment to each other and their patients. Recent findings from CDC on vaccination coverage among HCPs indicate that the 2015-2016 season showed the highest numbers vaccinated to date, even among those in ambulatory care.43 This clearly supports messaging that says to the public, “Your health care professional got vaccinated, shouldn't you?”

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Prepare Your Practice/Facility for Influenza Season

It is often hard to plan ahead when there are so many competing demands on HCPs, but time spent planning before influenza season will result in a healthier patient base and reduced demand for medical services during the winter respiratory virus season. It is important to start this preparation with staff; office or facility team buy-in is essential to success. The most effective and successful models for increasing vaccination rates in offices focus on delivery of frequent positive vaccine messages, even during routine telephone calls such as those to make an appointment, to repeated messaging and questioning during intake, and from all clinical staff. Standing orders improve vaccination coverage and should be considered in all practice environments.44

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Address Influenza Vaccination Coverage Gaps in African American and Hispanic Patients

Although there is a public health need to increase influenza vaccination coverage in the entire aged-65-years-and-older population, there are larger gaps in coverage for African American and Hispanic adults aged 65 years and older compared with the white, non-Hispanic population. Standardized offering of influenza vaccine has been shown to decrease disparities in vaccination coverage between white and non-white patient populations. Targeted efforts should be focused on identifying and addressing specific concerns or knowledge gaps that limit influenza vaccine uptake in these populations.

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Partner With and Use Community Resources

Check with your local public health department to see what vaccination services they offer and what information they can provide to help you prepare for influenza season. Although it would be optimal if every US health care practice could provide every type of influenza vaccine, this is often not the case. Many local pharmacies—both independent pharmacies and pharmacy chains—differ in the influenza vaccine options they have available at different points throughout the season. Influenza vaccines may also be available at senior and community centers, local public health clinics, and many retail stores. There are websites that provide up-to-date information on vaccine availability in local areas, including

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Summary: Tools Available to Improve Influenza Vaccination Coverage in Adults Aged 65 Years and Older

There are now more vaccine options available to the public than ever before, including high-dose and adjuvanted influenza vaccines approved specifically for adults aged 65 years and older, and in recent years, vaccine supply has met or exceeded demand. Medicare pays for influenza vaccines in full. Influenza vaccines are available in more locations than ever before, including the traditional doctor's office, public and community health clinics, pharmacies, and workplaces, among others.

Public health officials, medical professionals, professional societies, and others who are part of the US vaccine infrastructure must take advantage of every opportunity to provide optimal protection for adults aged 65 years and older and continue to work collaboratively to remove any ongoing barriers to vaccination.

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Frequently Asked Questions About Influenza Vaccination for Adults Aged 65 Years and Older

When Should I Get a Flu Vaccine?

You should get an annual influenza vaccine as soon as it is available in your area. However, as long as flu viruses are circulating, vaccination should continue throughout the flu season, even in January or later.

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Which Flu Vaccine Is Best for Me?

If you are aged 65 years or older, you may want to consider one of the newer flu vaccines specially approved for those 65 years or older, but getting any influenza vaccine is better than not getting vaccinated at all.

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Does the Flu Vaccine Work?

Yes, influenza vaccines work! How well they work can vary each year because different flu viruses circulate each year. In addition, vaccines may not prevent infection completely as we age, but getting vaccinated can make influenza less severe if you do get it and also lower your risk of hospitalization, heart attack, and death, among other serious complications.

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I Want the Special Vaccine for Adults Aged 65 Years and Older, But I Am Having Trouble Finding It. What Should I Do?

You can check to see which vaccines are available in your area, or you can call local pharmacies or senior centers. But do not delay in getting the vaccine that is available—it takes approximately 2 weeks for the influenza vaccine to become effective. A vaccination deferred is often a vaccine not received.

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I Am Allergic to Eggs. Can I Still Get a Flu Vaccine?

If you get only hives after exposure to eggs then you can get any flu vaccine. If you have had a more serious reaction, such as swollen lips and lightheadedness, or have trouble breathing and need emergency medical care, you should still get vaccinated, but either in a location where an HCP can monitor you for an allergic reaction after you have been vaccinated or with a special vaccine that is made with no egg allergens.

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I Have Never Had the Flu so Why Do I Need to Get a Vaccine?

There is no way to tell who will get the flu each year and there is no way to tell how severe the illness will be. Even if you feel perfectly healthy, you are at higher risk of serious outcomes from the flu as you get older, including being hospitalized or having a heart attack or a stroke.

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I Am Afraid the Vaccine Will Give Me the Flu

The influenza vaccine cannot give you the flu. People sometimes get sick shortly after they get the vaccine and they assume there is a connection. This is not from an influenza infection, but could be just part of how they feel as their body develops protection. Moreover, during the fall and winter respiratory virus season, people tend to get sick a lot. There is a chance that it happens close to when you got the shot, but that does not mean it is because of the vaccination.

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What Is the Difference Between the Newer Flu Vaccines for Adults Aged 65 Years and Older and the Standard Flu Vaccines?

As people age, their immune system may not respond as well, decreasing the body's ability to respond to vaccination. The influenza vaccines are designed to help improve the response of your immune system to vaccination and increase your chances of being protected against the flu.

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How Do I Know That the Newer Vaccines Are Safe?

Like all vaccines approved by the FDA, the newer influenza vaccines have undergone extensive testing and research.

For additional information, visit

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influenza; immunosenescence; cardiovascular outcomes; vaccines

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