Vaccines

Influenza

Updated: May 3, 2010

Table of Contents

    Understanding the Disease

    Influenza Viruses. Influenza viruses are grouped into 3 major types (A, B, and C), and strains are further divided into multiple subtypes depending on the source of the virus and the types of proteins on the outside of the virus particle.

    Although influenza B causes many children to be absent from school, influenza A viruses cause much of the severe illness during epidemics. All influenza viruses quickly change as people become immune to the strains circulating in the population so that immunity acquired one year will only partially protect for subsequent outbreaks.

    Influenza A viruses also have a remarkable potential for variation, mutating rapidly and also by being able to mix genetic material with influenza viruses from other species of birds and animals.

    Seasonal influenza. Influenza viruses can affect anyone, but rates of infection are highest among children. Serious illnesses and death also occur in all age groups but rates are greatest in persons over the age of 65 years and those who have chronic health problems. Epidemics of influenza occur during the winter months nearly every year but the peak of influenza epidemics can occur as late as April or May and is not predictable from year to year. Influenza is spread through coughing and sneezing, and is highly contagious, especially in childcare centers, schools, and nursing homes.

    Uncomplicated influenza generally comes on suddenly, and symptoms include muscle aches, fever, chills, headache, cough, and runny nose; it lasts for 3-7 days although cough can persist for about 2 weeks. The respiratory illnesses caused by influenza viruses are clinically difficult to distinguish from the illnesses caused by other respiratory infections. Young infants may have symptoms that mimic invasive bacterial infections with high fevers and fussiness, leading to hospitalization. Although most young children who are hospitalized with influenza virus infections are only in the hospital for a few days, some require treatment in an intensive care unit. The majority of children who are hospitalized for influenza infection are less than 5 years of age and a quarter of them are less than 6 months old.

    Influenza viruses can cause viral pneumonia, can make underlying medical conditions worse, and can lead to bacterial pneumonia, sinusitis and ear infections. Influenza virus infections have also been associated with inflammation of the heart and, brain swelling with liver failure.

    On average, influenza virus infections cause approximately 36,000 deaths and 148,000 hospitalizations each year in the United States.

    More than 90% of influenza-related deaths are in people aged 65 years or older. Although influenza-related deaths are much less common in children than the elderly, fatal cases have been increasingly recognized.

    Pandemic influenza. An influenza pandemic can occur when a new influenza A virus appears against which the human population has no immunity and when the new virus can spread from person to person. This can result in several, and simultaneous epidemics around the world. These virus strains may result from exchange of gene segments between human and avian or swine influenza viruses or from direct transmission of nonhuman viruses to humans.

    The severity of pandemics has varied substantially in the past. Depending on the virulence of the new virus—the degree of disease severity it causes—the numbers of deaths, hospitalizations, work that cannot be performed, and school absenteeism can differ a great deal from pandemic to pandemic.

    In 2009 a new influenza virus containing genetic information from swine, avian and human influenza viruses emerged called pH1N1 2009, and was the predominant strain that circulated in the 2009/2010 finluenza season. While not as severe during the first season as had been feared, this strain caused a disproportinate amount of illness and deaths in children, pregnant women and among those with underlying health problems such as asthma and obesity. The seasonal influenza vaccine for 2010/2011 will include this strain.

    Available Vaccines

    Abreviations: Trivalent inactivated influenza virus vaccine (TIV) and live attenuated trivalent influenza virus vaccine (LAIV).

    Product: Agriflu (TIV)
    Manufacturer: Novartis
    Year licensed: 2009
    Indications: For persons ages 18 years of age and older.

    Product: Fluzone High Dose (TIV)
    Manufacturer: Sanofi Pasteur
    Year Licensed: 2009
    Indications: For persons ages 65 years and older.

    Product: Afluria (TIV)
    Manufacturer: CS Limited
    Year Licensed: 2007
    Indications: For persons 6 months of age and older.

    Product: FluLaval (TIV)
    Manufacturer: ID Biomedical Corporation of Quebec
    Year Licensed: 2006
    Indications: For persons 18 years and older.

    Product: Fluarix (TIV)
    Manufacturer: GlaxoSmithKline
    Year licensed: 2005
    Indications: For persons ages 3 years or older.

    Product: FluMist (LAIV)
    Manufacturer: MedImmune Vaccines
    Year Licensed: 2003
    Indications: For persons 2 through 49 years of age.

    Product: Fluvirin (TIV)
    Manufacturer: Novartis
    Year Licensed: 1988
    Indications: For persons 4 years of age and older.

    Product: Fluzone (TIV)
    Manufacturer: Sanofi Pasteur
    Year Licensed: 1978
    Indications: For persons 6 months of age and older.

    FluMist, Agriflu, and Fluarix do not contain thimerosal. Afluria, Fluvirin and Fluzone are available with reduced thimerosal formulation.

    History of the Vaccine

    Influenza vaccines have been used since 1945. Each year, the vaccines contain three virus strains that are expected to affect the United States in the upcoming winter; in 2009 there was also a monovalent vaccine prepared that was deployed separately from the seasonal vaccine because the newly recognized strain appeared after it was too late to be included in the 2009 seasonal vaccines.

    Until recently, all available influenza vaccines were trivalent inactivated (killed) influenza virus vaccines (TIV). Inactivated influenza virus vaccines cannot cause influenza. TIV came in whole-virus and split-virus forms prior to 2001; however, because of fewer side effects, including fever and reactions at the injection site, only split-virus TIVs are currently available in the U.S. In June of 2003, a live, attenuated, cold adapted, temperature sensitive, trivalent influenza virus vaccine (LAIV) was licensed in the United States. The temperature sensitive type A and B strains of influenza virus contained in LAIV replicate (multiply) in the nasal passages but not in the lower respiratory tract.

    Due to the change in the types of influenza viruses circulating each year, some of the virus components of the influenza vaccines must be changed as well.

    In 2010, a new high dose formulation of TIV will be available for use in people age 65 years and older. This Fluzone High-Dose contains four times the amount of influenza antigens than the other TIVs in order to induce a higher immune response in older people who are most susceptible to the complications of seasonal influenza but who respond less well to the vaccine. This vaccine appears to have slightly higher rates of local reactions but may afford greater protection to those in this age group.

    Who Should and Should Not Receive the Vaccine

    All Americans more than 6 months of age should be immunized annually. 

     

    Who should not receive influenza vaccine:

    • Infants younger than six months of age.
    • People who have had an anaphylactic reaction (allergic reactions that cause difficulty breathing, which is often followed by shock) to eggs, egg products, or other components of the flu vaccine. There are antiviral agents which doctors can prescribe as an alternative for preventing influenza in such people.
    • Children younger than two years of age and adults over 49 years of age should not receive LAIV because safe use in these age groups has not been established.
    • LAIV should not be given to children and adolescents (2-17 years of age) receiving aspirin or aspirin-containing medications, because of the complications associated with aspirin and wild-type influenza virus infections in this age group.
    • People with a history of asthma or other reactive airway diseases should not be given LAIV.
    • People with chronic underlying medical conditions that may predispose them to severe influenza infections should also not be given LAIV. For these people, TIV is indicated.
    • LAIV should not be given to pregnant women.
    • LAIV should not be given to people with a history of Guillain-Barre syndrome.
    • LAIV should not be given concurrently with other live-virus vaccines.
    • People with acute serious illness with fever
    • People who are moderately or severely ill should consult with their physician before receiving any vaccine
    • Under no circumstances should LAIV be given by injection.

    Influenza immunization is recommended by:

    • Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention
    • American Academy of Family Physicians
    • American Academy of Pediatrics
    • American Thoracic Society

    The summary of adolescent/adult immunization recommendations can be found at the CDC site.

    Dose Schedule

    TIV is given by the intramuscular route; LAIV is administered as a nasal spray. The formulation of influenza vaccines differ according to the manufacturer. TIV formulations in multidose vials contain thimerosal as a preservative.

    When young children (six months until nine years old) are vaccinated against influenza for the first time, they should receive two doses of age-appropriate influenza vaccine given one month apart. Those children who received only one dose in their first year of vaccination should receive two doses in the following year. Two doses administered 4 weeks apart are also recommended for children 2 -8 years of age who are receiving LAIV for the first time. For children 6-35 months of age, a half dose (0.25 ml) of TIV (injected) is recommended, in contrast to 0.5 ml which is the usual dose for everyone over three years of age.

    In the United States, Fluzone and Afluria may be administered to children as young as six months of age. Fluarix should only be given to children 3 years of age and older whereas Fluvirin should only be given to children four years of age and older because their efficacy and safety in younger people have not been demonstrated. Flulaval and Agriflu are not licensed for use in children but are licensed for adults 18 years of age and older. High-dose Fluzone is indicated only for persons 65 years of age and older.

    LAIV should only be given to healthy children and adolescents, ages 2-17 years, and healthy adults, ages 18-49.

    Ideally, people should receive their annual influenza vaccine from the beginning of October through November each year, prior to the influenza season, which generally peaks during late December through March. However, vaccination later in the season is considered worthwhile.

    Effectiveness of the Vaccine

    Each year, the influenza vaccine contains three virus strains, representing the influenza viruses thought to be the most likely to circulate in the United States in the upcoming winter.

    When the match between the virus strains in the vaccine and the circulating viruses is close, the vaccine prevents illness in up to 90% of healthy adults under the age of 65. Among elderly people, the vaccine is about 30-70% effective in preventing disease, but it is 50-60% effective in preventing hospitalization and 80% effective in preventing influenza-related death in the elderly.

    The vaccine protects between 45% and 90% of healthy children from getting influenza. Studies indicate that the older and healthier children who have received the influenza vaccine are, the more likely they will be protected. Influenza vaccination has also been shown to decrease middle ear infections among young children by about 30%.

    One goal for widespread, universal, influenza vaccine utilization in the United States is to decrease the transmission of influenza viruses. Epidemiologic studies have demonstrated that children have the highest rates of influenza virus infections, suggesting that universal immunization of children could result in transmission of these viruses within communities, from persons providing care or who are household contacts of people who are high risk for complications from influenza (including young infants less than 6 months of age (for whom there is no effective vaccine and no licensed treatment)), those with chronic diseases and those who are older than 50 years of age (especially those who are over 65 years of age).

    Of particular concern are healthcare workers who also commonly acquire influenza virus infections and who can transmit influenza viruses in hospitals and long-term care facilities. Vaccination of healthcare workers has been associated with decreased deaths among nursing homes, for example.

    Known Side Effects

    The majority of those immunized with TIV will have no adverse reactions. Of those who do have a side effect, most will have soreness or tenderness at the injection site. Fewer than 1% of adults immunized will also experience fever, chills, or a general sense of feeling unwell that lasts one to two days. Children are more likely to experience these symptoms.

    In very rare cases (far less than 1 out of 10,000), serious reactions can occur. People who have an allergy to eggs (which are used in making the vaccine) or any component of the vaccine are at greater risk for a serious allergic reaction. If you or your child has developed hives or swollen lips or tongue; has had trouble breathing; or has collapsed after eating eggs or receiving a previous dose of influenza vaccine, consult with your healthcare provider to see if the vaccine should be given.

    Because of a slight increase in the frequency of Guillain-Barre Syndrome [GBS] (a progressive disorder affecting the nervous system) associated with the 1976 swine flu vaccine, subsequent flu vaccines have been closely monitored. It has been estimated that about one case of GBS may occur per million persons immunized with TIV, although these cases may not be related to TIV. If a person is not at high risk for getting complications from influenza, a person who developed GBS within six weeks of a previous influenza shot should avoid subsequent influenza shots. If the risk from influenza is high, they should be vaccinated with an age-appropriate inactivated influenza vaccine because the established benefits of the vaccine justify vaccination. LAIV should not be given to individuals who have a history of GBS because safety in those persons has not been investigated.

    Related Issues

    Influenza vaccines given as a nasal spray are being used for adults in Russia, and have been under development in the U.S. since the 1960’s. LAIV administered as a nasal spray was approved by the FDA in June of 2003. It is the first nasally administered vaccine to be marketed in the United States and the first live virus influenza vaccine approved in the U.S. The possible advantages of this type of vaccine are that it is easy to administer, has the potential to induce a broad mucosal and systemic immune response, and has been shown to be approximately 87% effective in children. Although TIV and LAIV appear to have similar effectiveness and safety profiles, no study has directly compared the efficacy or effectiveness of TIV and trivalent LAIV.

    Persons 65 years and older are at increased risk for hospitalization and death from seasonal influenza but unfortunately they respond less well to the TIV vaccine than do other age groups. In 2010, a new high-dose TIV will be available which may provide improved immunity for people in this age group. The Centers for Disease Control and Prevention has not expressed a preference for any influenza vaccine, however, because studies to determine whether the high dose TIV are more effective are not yet available.

    Key References and Sources of Additional Information

    • American Academy of Pediatrics, Committee on Infectious Diseases. (2006). Influenza. In Red Book: Report of the Committee on Infectious Diseases. Elk Grove Village, IL.
    • Centers for Disease Control and Prevention (CDC). (2010). ACIP recommendations for influenza vaccine will be published in June 2010. Provisional recommendations are available here.
    • CDC. (2009). Prevention and control of influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 58 (RR-08).
    • CDC. 2010. Licensure of a high-dose inactivated influenza vaccine for persons aged >65 years (Fluzone High-Dose) and guidance for use—United States, 2010. MMWR 59(16):485-6.

    CDC Information

    http://cdc.gov/vaccines/pubs/vis/default.htm#flu