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Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations
Miranda Wilhelm, PharmD
Participating Faculty
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Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations

Miranda Wilhelm, PharmD
Influenza affects millions of people in the United States each year. Older patients are particularly at risk for infection, hospitalization, and death due to influenza-related complications, such as pneumonia. One of the best ways to avoid becoming ill is to have the annual influenza vaccination. Unfortunately, immunization rates are poor in the older adult population, at about 65% each year. Vaccine effectiveness in this population is reduced because of lower seroconversion rates that arise from poorer immunologic response to vaccination. Several new influenza vaccines that have been introduced to the market in recent years attempt to boost immune response, including high-dose formulations and adjuvanted and recombinant vaccines. Managed care pharmacists need to understand the utility of these new agents in populations 65 years or older. This supplement highlights the impact of influenza on older patients, the features of new vaccine preparations, and the economic burden of influenza.
Am J Manag Care. 2018;24:-S0
Influenza is an acute respiratory infection found worldwide and known to infect humans, other mammals, and birds. In the Northern Hemisphere, outbreaks of influenza occur seasonally, primarily from December to March. It is a self-limiting disease in most individuals. The classic acute flu-like symptoms develop in about 50% of people and include fever (usually 101°- 102° F), myalgia, sore throat, nonproductive cough, and headache.1 It is transmitted via respiratory droplets from sneezing and coughing, starting approximately 1 to 2 days before symptoms appear up to 5 to 10 days later, but the infection may last longer in very young, elderly, and immunocompromised persons. Secondary complications, such as pneumonia, bronchitis, and sinus and ear infections, as well as exacerbations of chronic medical conditions, are sources of considerable morbidity and mortality.1

Adults 65 years or older represent a large at-risk population. These patients account for most seasonal influenza-related hospitalizations and related complications.1 Most seasonal influenza-related deaths occur in adults 65 years or older. While the percentage of US adults 65 years or older receiving an influenza vaccination is higher than in younger age groups, it remains that only 65.3% of these adults received a flu vaccination in the last 12 months, leaving about 35% of all older adults unprotected against influenza.1

Influenza From Then to Now

Pandemics are worldwide events; epidemics and outbreaks are localized. The first recognized pandemic occurred in 1580, spreading from Asia to Asia Minor, North Africa, Europe, and North America.2 The pandemic of 1918 sickened half the world’s population and killed approximately 50 million people, about 3% of the world’s population.2 Other pandemics of the 20th century include the 1957 Asian flu and the 1968 Hong Kong flu; the most recent pandemic, the swine flu, occurred in 2009. In the latter, most fatalities occurred in Africa (an estimated 151,700 people) and Southeast Asia (an estimated 575,400).3

Although available vaccines reduce the prevalence and risk of contracting influenza, vaccination uptake is not optimal, leaving many millions at risk of infection. Each year, the CDC estimates the impact of influenza on the US population, based on models that incorporate reported death rates (influenza and influenza-related), vaccination rates, and vaccine effectiveness, to arrive at ranges of persons affected, persons hospitalized, deaths, and illness averted. These ranges can be quite large, depending on the flu season. Since 2010, there have been 9.2 million to 35.6 million cases of influenza in the United States, causing an estimated 140,000 to 710,000 hospitalizations and 12,000 to 56,000 deaths in each.1 The total economic burden of annual influenza epidemics using projected statistical life-values is nearly $100 billion.4

Severity of Influenza in Older Patients

The term influenza was first used in the scientific literature in 1650 and the first influenza virus was isolated in 1931.2 There is now a much greater understanding of influenza, which has allowed us to develop vaccines and the tools necessary to care for the most severely affected patients.

Populations at Risk

For most people, influenza is a relatively mild illness that usually does not require extensive medical care. However, some groups of people are at higher risk of developing influenza-related complications that require hospitalization and may lead to death. People in these groups include infants and young children 6 months to 5 years, older adults (≥65 years of age), pregnant women, residents of long-term care facilities, Native Americans, and those with certain chronic medical conditions (eg, asthma, diabetes, heart disease).1 The focus in this supplement will be on elderly patients.

Elderly Populations

During a typical influenza season, most people infected by the virus recover in 3 to 10 days. However, elderly persons bear the greatest burden of morbidity and mortality of any group, with 54% to 70% of seasonal influenza-related hospitalizations and 71% to 85% seasonal influenza-related deaths.1

Older patients are less likely to display classic influenza symptoms than are younger patients. Fever is often not present. Instead, many older patients present with exacerbations of pre-existing comorbidities, such as dyspnea or cough. In a survey of laboratory-documented influenza in veterans older than 50 years with chronic obstructive pulmonary disease (COPD), respiratory symptoms (cough, sputum production, and dyspnea) occurred in more than 90% of patients, fever in 68%, and myalgias in 81%.5

The elderly population is afflicted by significant comorbidities, many of which are, themselves, risk factors for influenza-related complications. These include chronic lung disease (eg, COPD), heart disease (eg, heart failure and coronary artery disease), endocrine disorders (eg, diabetes), kidney and liver disorders, weakened immune system due to disease or medication (eg, cancer therapy, chronic steroid use), and extreme obesity (body mass index ≥40).1

Immunosenescence

With advancing age comes declining systemic immunity.6 Immunosenescence describes the age-related decline of both innate and adaptive immunity, leaving the person more susceptible to disease caused by pathogens, including influenza and those causing influenza-related complications. Immunosenescence is suspected to be the cause of the counter-intuitive observation that, in pandemics, younger people are afflicted with higher mortality and morbidity. It has been postulated that younger people, with a more robust immune system, produce a stronger reaction and trigger a life-threatening cytokine storm, although older people do not.2 Thus, although older people are less likely to die from influenza, they are more likely to become infected in nonpandemic years. Unfortunately, influenza infection opens the door to other, opportunistic infections that, ultimately, are responsible for most deaths from influenza during both pandemics and seasonal disease spread.

Influenza Virus

Influenza is a collection of related Orthomyxoviridae viruses with varying characteristics, such as preferred host. Four types exist: Type A infects humans, swine and other mammals, and birds; types B and C infect humans; and type D affects cattle and does not affect humans.1 Types A and B are associated with considerable morbidity and mortality in humans, while type C typically causes only mild symptoms.

Structure and Nomenclature

Influenza virus particles have a capsid composed of lipid and protein, surrounding a core of RNA and protein (Figure 1).7 The capsid proteins are primarily hemagglutinin and neuraminidase, which contain the antigenic determinants.

Subtypes of influenza type A viruses are distinguished by the specific isoform of hemagglutinin and neuraminidase on the virion surface. There are 18 different hemagglutinins (H1-H18) and 11 different neuraminidases (N1-N11).1 The H/N designation gives rise to the familiar “H1N1,” “H3N2,” and similar names of these viruses. The full name for an influenza virus includes the antigenic type (A, B, C, D), lineage or original host species (eg, bird, swine, bat, with the exception of “human,” which is never listed), geographic origin (if known), strain number (ie, sub-subtype), year the virus was isolated, and the H/N subtype designation (Figure 2).1,8

Influenza Genome

Influenza is a segmented RNA virus. Eight different RNA strands are within each virion, much like the human nucleus has 23 different chromosomes.7 Each RNA strand encodes 1 of 8 influenza genes that produce 11 proteins. The segmented nature of the influenza genome allows for shuffling of genes, when multiple influenza viruses are present at the same time within a cell. This can occur in numerous hosts, such as birds and swine. The resulting virus has never been seen in most hosts. This feature is critical to the high-level virulence seen in epidemics and pandemics. The Spanish flu of 1918 was a product of a swine hemagglutinin inserted into a human virus.

“Drift” Versus “Shift”

Currently circulating influenza A viruses include the H1N1 and H3N2 subtypes and circulating B virus lineages include Yamagata and Victoria. However, influenza changes and evolves readily. Small changes are known as “antigenic drift” and result from, for instance, single nucleotide changes in the influenza genome.1 Immunologically, viruses that experience antigenic drift will be very similar to the original virus and are likely to have similar (but not identical) antigenic properties. A hemagglutinin 3 can drift and become a hemagglutinin 3 variant. An immune system that has seen 1 virus could possibly react against the new virus (ie, “cross-protection”).1

With each incremental drift, the likelihood of cross-protection is reduced. Eventually, enough drift occurs that a person’s immune system will not recognize the newest version of the virus.1 When this happens, the person can become ill again with the same H/N influenza variant.

Antigenic shift, on the other hand, is a large change in the genome of the virus; it occurs infrequently.1 These changes typically result in new and exceptionally virulent strains of influenza, and they can cause pandemics. Antigenic shift involves reassembly of the virus from 1 or more types of influenza into a chimeric virus, having parts from multiple sources.

Each year, the CDC analyzes more than 1 million patient specimens and sequences the genomes of 6000 viruses to prepare up to 50 viruses for possible use in vaccine production.1 They then take their best reasoned guess of which viruses will be dominant the following influenza season.

Complications of Influenza Infection

Influenza infection is characterized as either uncomplicated, meaning that illness is confined to symptoms of influenza alone, or complicated, meaning that secondary illness or infection sets in.9

Pneumonia

Pneumonia is the most common serious complication. As a result of weaker immunity and higher incidence of comorbidities, the elderly are more likely to be afflicted with influenza-related complications, particularly pneumonia.1 Factors associated with an increased risk of developing pneumonia include age  75 years or older, nursing home residence, chronic lung disease, immunosuppression, and asthma.10 Patients with an influenza infection and pneumonia were significantly more likely to require intensive care unit (ICU) admission (27% vs 10%) and mechanical ventilation (18% vs 5%), and to die (9% vs 2%), as compared with patients without pneumonia.

 
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