Influenza outbreaks of varying severity occur every winter. In recent U.S. influenza epidemics, about 20,000 deaths were estimated to be associated with influenza. The rate climbed to more than 40,000 excess deaths in selected epidemics.1 Furthermore, during some epidemics of influenza type A, there have been approximately 172,000 extra hospitalizations associated with influenza and pneumonia.2 The cost of a severe influenza epidemic in the United States has been estimated to be almost $12 billion.3 Influenza outbreaks strain the health care system. In 1989, 11 percent of office visits to family physicians during the peak of the influenza season were for influenza-like illness.4
Significance of High-Risk Conditions and Age on Influenza Morbidity
The fatality rate from influenza begins to rise in mid-life (about 45 years of age) and is highest in persons who have chronic medical conditions, such as chronic obstructive lung disease, cardiovascular disease and diabetes mellitus. The elderly, partly because of their high rate of chronic medical conditions, are the population with the highest age-specific case-fatality rate from influenza and suffer most of the deaths associated with influenza. However, influenza has a higher case-fatality rate in middle-aged persons with chronic medical conditions than in persons about 65 years of age who are well (Table 1).
Many persons have an underlying medical condition that places them at high risk for complications from influenza. Data from the 1995 National Health Interview Survey show that 24 percent of patients 50 through 64 years of age have such an underlying medical condition (unpublished data, Centers for Disease Control and Prevention [CDC]). The incidence of such conditions increases with age.
Efficacy of Influenza Vaccine
EFFICACY IN HEALTHY ADULTS UNDER 65 YEARS OF AGE
Because influenza rarely causes death in healthy persons under 65 years of age, the outcomes are based on morbidity indexes such as illness, lost work time and physician visits. When there is a good match between vaccine and circulating viruses, influenza vaccine has been shown to prevent illness in approximately 70 to 90 percent of healthy persons less than 65 years of age.1 When the match between vaccine and circulating virus is poor, efficacy is less. A study of working adults 18 to 64 years of age found that influenza vaccination reduced episodes of upper respiratory illness by 25 percent (105 versus 140 episodes per 100 subjects; the number needed to treat to prevent one upper respiratory illness was 2.9); reduced the amount of sick leave taken from work associated with upper respiratory illness by 43 percent (70 versus 122 days per 100 subjects); and reduced visits to physicians' offices for upper respiratory illness by 44 percent (31 versus 55 visits per 100 subjects; the number needed to treat was 4.2 to prevent one physician visit).6
EFFICACY IN ELDERLY ADULTS
Elderly persons and those with certain chronic diseases may develop lower postvaccination antibody titers than healthy young adults. However, even if influenza develops despite vaccination, the vaccine lowers the risk of severe disease and complications. This is true for elderly persons living in nursing homes and for those living in the community. Among elderly persons residing in nursing homes, influenza vaccine can be 50 to 60 percent effective in preventing hospitalization and pneumonia, and 80 percent effective in preventing death, even though its efficacy in preventing influenza illness may be in the range of 30 to 40 percent.1 Furthermore, in one study, influenza vaccination resulted in a 37 percent reduction in hospitalization associated with congestive heart failure and was 54 percent effective in reducing mortality from all causes.7
Cost-Effectiveness of Influenza Vaccine
In noninstitutionalized elderly adults, it has been documented that influenza vaccination reduced the costs of hospitalization associated with acute and chronic respiratory disease and congestive heart failure, and resulted in a direct savings of $117 per person vaccinated per year.7 In working adults 18 to 64 years of age, the cost savings were estimated at $46.85 per person vaccinated.6
Limitations of a High-Risk Strategy for Adults 50 to 64 Years of Age
Although many persons 50 to 64 years of age have high-risk conditions such as asthma, diabetes mellitus or heart disease, a minority are vaccinated despite recommendations supporting vaccination from the American Academy of Family Physicians (AAFP), the CDC and other groups. In fact, data from the 1995 National Health Interview Survey show that only 38 percent of those 50 through 64 years of age who were at high risk for complications from influenza were vaccinated.8 Manual or computerized reminder systems based on high-risk conditions are more difficult to implement than those based on age. Many persons with a high-risk condition do not know that they have a high-risk condition. High-risk vaccination strategies for other immunizations have had limited success.
Indications for Influenza Vaccine
In 1999, the AAFP lowered the age recommendation for routine influenza vaccination and, to the author's knowledge, it is the first national organization to do so. The AAFP now recommends that all persons aged 50 years and older receive an annual influenza vaccination. In the event of a vaccine shortage, persons with high-risk conditions and the elderly should receive the first priority for vaccination. Physicians may require time and resources to incorporate this new vaccination effort into practice.
Influenza vaccine continues to be recommended for patients who are six months of age and older with chronic pulmonary, cardiovascular, renal, metabolic or immunosuppressive diseases (Table 2). Because the target groups for influenza and pneumococcal vaccines overlap, providers should assess the need for pneumococcal vaccination when administering influenza vaccine to high-risk persons.
|Categories and specific indications|
|Health care worker|
|Alcoholism and alcoholic cirrhosis|
|Long-term aspirin therapy in children less than 18 years of age (risk associated with Reye's syndrome)|
|Cardiac disease that alters or potentially alters hemodynamics|
|Immunocompromised patients (congenital immunodeficiency, malignancy, HIV, transplantation, immunosuppressive therapy)*|
|Chronic metabolic diseases that increase the likelihood that infections will be more severe|
|Pregnancy in women who have medical conditions that increase their risk for complications from influenza, regardless of trimester|
|Pregnancy beyond the first trimester during the influenza season|
|Chronic pulmonary disease, including asthma and chronic obstructive pulmonary disease|
|Chronic renal disease|
|Close contacts at high risk|
|Household contacts of persons at high risk for influenza|
|Residents of institutions for developmentally disabled or mentally handicapped persons|
|Residents of nursing homes and chronic care facilities|
Persons who are in contact with chronically ill patients, such as health care providers and home care providers, should receive influenza vaccine yearly so that they are not a source of transmission. To reduce transmission in crowded environments, residents of nursing homes and other chronic care facilities should be immunized.
Administration of Influenza Vaccine
Beginning each September, when vaccine for the upcoming influenza season becomes available, persons at high risk who visit physicians should be offered influenza vaccine so that vaccination opportunities are not missed. The optimal time for organized vaccination campaigns for persons in high-risk groups is usually from October through mid-November.
Inactivated influenza vaccine is administered by intramuscular injection. Influenza vaccine can be administered simultaneously—but at different injection sites—with pneumococcal vaccine or routine childhood vaccines.
Administration of influenza vaccine to children is more complex. Children who receive inactivated influenza vaccine should be given a split virus vaccine because it has fewer adverse reactions than inactivated whole virus vaccines. Previously unvaccinated children less than nine years of age should receive two doses at least one month apart in the first year that they receive inactivated influenza vaccine. The correct dosage varies by age (Table 3). Inactivated influenza vaccine is not recommended for use in infants younger than six months of age.
Contraindications and Adverse Reactions
The main contraindication to influenza vaccine is anaphylactic reaction to eggs or other vaccine components. Persons who can eat eggs without experiencing a reaction generally can be vaccinated. Skin testing can help differentiate those who have a true immediate hypersensitivity reaction to egg protein from those who do not. A protocol is available for vaccination of persons who have a true allergy to egg protein yet need influenza vaccine because of high-risk conditions.9 This protocol should be used only in a setting where emergency equipment is available.9
Influenza vaccine contains small amounts of thimerosal, a mercurial antibacterial agent that acts as a preservative. Severe allergy to this component is rare. Because influenza vaccine is given to persons who are six months of age and older, and because the concerns about thimerosal are based on young infants with relatively small body weights, influenza vaccines containing thimerosal continue to be recommended. Allergy to duck dander or duck meat is not a contraindication. Influenza vaccination should be delayed in persons with an acute febrile illness. A person who has a contraindication to influenza vaccine may be a candidate for prophylaxis with amantadine (Symmetrel) or rimantadine (Flumadine).
Possible adverse events associated with influenza vaccine include local reactions at the injection site such as soreness and, occasionally, fever and myalgia. Because the influenza vaccine is not a live vaccine, it cannot cause influenza. The current vaccines are considerably purer than vaccines produced before 1968 and cause far fewer adverse events. From October 1976 through January 1977, a vaccine containing influenza A/New Jersey was associated with Guillain-Barré syndrome10; the attributable risk was estimated at 8.8 cases per 1 million vaccinations. Studies since the use of the 1976 swine influenza vaccine are mixed, depending on the year, with some years not showing an increased risk and others suggesting a slight increase. If influenza vaccine increases the risk of Guillain-Barré syndrome, the risk is quite small, on the order of one to two additional cases per 1 million persons vaccinated. There is good evidence that a number of infectious diseases, particularly Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus and Epstein-Barr virus provoke Guillain-Barré syndrome.