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Influenza Update

Sharon A. Sanders, RN

Margaret McClure, AA

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The information in this course is taken primarily from the Centers for Disease Control and Prevention, Prevention and Control of Influenza, Recommendations of the Advisory Committee on Immunization Practices (ACIP).

THE IMPACT OF INFLUENZA

Influenza (the "flu") is a contagious respiratory illness caused by influenza viruses. It can cause mild to severe illness and, in some instances, lead to death. Most healthy people recover from the flu without complications. Some people, including older adults, young children, and people with certain health conditions, are at high risk for serious complications from the flu.

Flu usually starts suddenly and may include these symptoms:

• Fever (usually high)
• Headache
• Tiredness (can be extreme)
• Cough
• Sore throat
• Runny or stuffy nose
• Body aches
• Diarrhea and vomiting (more common in children)

These symptoms are referred to as "flu-like symptoms." Other illnesses, including the common cold, can have similar symptoms.

Human influenza is transmitted primarily via large, virus-laden droplets that are generated when infected individuals cough or sneeze. These large droplets may be deposited directly onto the mucosal surfaces of the upper respiratory tract of susceptible individuals who are near the droplet source. Transmission may also occur through direct or indirect contact with infectious respiratory secretions. It is possible for a person to be actively transmitting the flu before they are aware they are sick.

Epidemics of influenza typically occur during the winter months. In the United States, from 1990 to 1999, influenza was responsible for approximately 36,000 deaths per year. Influenza viruses also can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide.

Influenza viruses cause disease among all age groups. Rates of infection are highest among children, but rates of serious illness and death are highest among people over 65 years of age and people of any age who have medical conditions that place them at increased risk for complications from influenza.

Influenza vaccination is the primary method for preventing influenza and its severe complications. It is associated with reductions in influenza-related respiratory illness and physician visits among all age groups. Vaccination is also associated with decreased hospitalization and death among people at high risk, otitis media among children, and work absenteeism among adults.

In healthy adults under 65 years of age, influenza vaccine typically prevents influenza illness among approximately 70% to 90% when the vaccine and circulating viruses are antigenically similar. Also, when the vaccine and circulating viruses are well-matched, vaccination of healthy adults results in decreased work absenteeism and decreased use of healthcare resources, including use of antibiotics.

Among adults over 65 years of age, with and without high-risk medical conditions (eg, heart disease, diabetes), influenza vaccine helps prevent secondary complications and reduce the risk for influenza-related hospitalization and death. Older people and those with certain chronic diseases might have lower post-vaccination antibody titers than healthy young adults and can remain susceptible to influenza virus infection and influenza-related upper respiratory illness.

Among older people who are not living in nursing homes or similar facilities, influenza vaccine is 30% to 70% effective in preventing hospitalization for pneumonia and influenza. Among older people who reside in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications, and deaths. In this population, the vaccine can be 50% to 60% effective in preventing influenza-related hospitalization or pneumonia and 80% effective in preventing influenza-related death, although the effectiveness in preventing influenza illness often ranges from 30% to 40%.

Influenza vaccination levels increased substantially during the 1990s. However, further improvements are needed, especially in vaccine coverage for children aged 6 to 23 months, for healthcare workers, for people under the age of 65 who are at risk for influenza-related complications, and for all racial and ethnic groups over the age of 65.

The CDC's Advisory Committee on Immunization Practices (ACIP) recommends using strategies to improve vaccination levels, including using reminder/recall systems and standing orders programs. Vaccination remains the cornerstone for the control and treatment of influenza, and it can be supported as needed by the use of antiviral medications.

THE BIOLOGY OF INFLUENZA

Two types of influenza viruses cause epidemic human disease: Influenza A and B. Influenza A viruses are categorized into subtypes on the basis of two surface antigens: hemagglutinin (H) and neuraminidase (N). Antigens are substances that the body recognizes as foreign, and thus they provoke an immune response. Influenza B viruses are not categorized into subtypes.

Since 1977 influenza A(H1N1) viruses, influenza A(H3N2) viruses, and influenza B viruses have been in global circulation.

In 2001 influenza A(H1N2) viruses, which probably emerged from human A(H3N2) and A(H1N1) viruses, began circulating widely.

The influenza A and B viruses are further separated into groups on the basis of antigenic (immune response) characteristics. New influenza virus variants result from frequent antigenic drift. Antigenic drift is the tendency of a virus to alter its genetic makeup, which causes production of new antibodies to combat the altered virus. When this occurs, a new vaccine is required. Influenza B viruses undergo antigenic drift less rapidly than influenza A viruses.

A person's immunity to the surface antigens, including hemagglutinin, reduces the likelihood of infection and the severity of the disease if infection occurs. An antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibodies to one antigenic variant of influenza virus may not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason that each year the new strains must be included in the latest influenza vaccine.

SIGNS AND SYMPTOMS

Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms such as fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis. Among children, otitis media, nausea, and vomiting are also commonly reported with influenza illness. Respiratory illness caused by influenza is difficult to distinguish from illness caused by other respiratory pathogens on the basis of symptoms alone.

In the absence of a lab-confirmed diagnosis, patient symptoms must be assessed. A study among older, nonhospitalized clients determined that symptoms of fever, cough, and acute onset had a likelihood of 30% for influenza, whereas a study of hospitalized older clients with chronic cardiopulmonary disease determined that a combination of fever, cough, and illness of less than seven days was about 75% predictive for influenza.

A study among vaccinated older adults with chronic lung disease reported that cough was not predictive of influenza infection, although one-half to two-thirds of those having a fever (or feverishness) were likely to have influenza infection. Influenza illness typically resolves after a limited number of days for the majority, although cough and malaise can persist for more than two weeks.

Among certain individuals, influenza can exacerbate underlying medical conditions such as pulmonary or cardiac disease, lead to secondary bacterial pneumonia or primary influenza viral pneumonia, or occur as part of a co-infection with other viral or bacterial pathogens. Young children with influenza infection can have initial high fevers that mimic bacterial sepsis; less than 20% of children hospitalized with influenza have febrile seizures. Influenza has also been associated with encephalopathy, transverse myelitis, Reye syndrome, myositis, myocarditis, and pericarditis.

The incubation period for influenza is 1 to 4 days, with an average of two days. Adults typically are infectious from the day before symptoms begin through approximately 5 days after onset of illness. Children can be infectious for more than ten days, and young children can shed virus for up to six days before onset of illness. Severely immunocompromised individuals can shed virus for weeks or months.

THE RISKS FOR COMPLICATIONS

The risks for complications, hospitalizations, and deaths from influenza are higher among adults over the age of 65, young children, and individuals of any age with certain underlying health conditions. Risks are lower among healthy older children and younger adults. Estimated rates of influenza-associated hospitalizations have varied substantially by age group in studies conducted during influenza epidemics.

Among children under the age of 4, hospitalization rates have ranged from approximately 500 per 100,000 for those with high-risk medical conditions to 100 per 100,000 for those without high-risk medical conditions. In the under 4 age group, hospitalization rates are highest among children aged 0 to 1 year and are comparable to rates reported among adults over the age of 65.

Since the 1968 influenza A(H3N2) virus pandemic, the greatest numbers of influenza-associated hospitalizations have occurred during epidemics caused by type A(H3N2) viruses, with an estimated average of 142,000 hospitalizations per year. Influenza-related deaths can result from pneumonia as well as from exacerbations of cardiopulmonary conditions and other chronic diseases.

Older adults account for more than 90% of deaths attributed to pneumonia and influenza. In a recent study of influenza epidemics, approximately 19,000 influenza-associated pulmonary and circulatory deaths per influenza season occurred during 1976–1990 compared with approximately 36,000 deaths during 1990–1999. The number of influenza-associated deaths may be increasing, in part because the number of older adults is increasing.

Influenza seasons in which influenza A(H3N2) viruses predominate are associated with higher mortality; influenza A(H3N2) viruses predominated in 90% of influenza seasons during 1990–1999, compared with 57% of seasons during 1976–1990. Deaths from influenza are uncommon among children with and without high-risk conditions, but they do occur.

INFLUENZA VACCINES

Two types of vaccine are available in the United States: Trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV). TIV contains dead virus. LAIV contains attenuated (or weakened) viruses. The weakened strains of LAIV do not usually cause illness because they have lost virulence. However, they may possibly reproduce and cause disease, especially in persons with weakened immune systems. Both can reduce the risk for virus infection and its complications.

Vaccination coverage can be increased by administering vaccine to patients during hospitalizations or routine healthcare visits. Making vaccine available before the influenza season at pharmacies, grocery stores, workplaces, or other locations in the community reduces the need for special visits to physicians' offices or clinics.

Achieving increased vaccination rates among individuals living in closed settings (eg, nursing homes, other chronic-care facilities) and among staff can reduce the risk for outbreaks, especially when vaccine and circulating strains are well-matched. Vaccination of healthcare workers and others in close contact with those at increased risk for severe influenza illness also can reduce transmission of influenza and subsequent complications.

Comparing TIV and LAIV

Administered annually to provide optimal protection, both TIV and LAIV provide effective prevention against influenza. Both vaccines contain strains of influenza viruses antigenically equivalent to the annually recommended strains: one influenza A(H3N2) virus, one A(H1N1) virus, and one B virus. Each year, based upon global surveillance for influenza viruses and the emergence and spread of new strains, one or more virus strains might be changed. Viruses for both vaccines are grown in eggs. The vaccines do differ in several aspects.

TIV contains killed viruses, and thus cannot produce signs or symptoms of influenza virus infection. In contrast, LAIV contains live, attenuated viruses and has a potential to produce mild symptoms related to influenza virus infection. LAIV is administered intranasally by sprayer; TIV is administered intramuscularly by injection. LAIV is more expensive than inactivated influenza vaccine. LAIV is Food and Drug Administration (FDA)–approved only for use among healthy individuals aged 5 to 49 years; TIV is FDA-approved for use among those over 6 months of age, including those who are healthy and those with chronic medical conditions.

Effectiveness of TIV

Over time, the effectiveness of TIV has been amply demonstrated. Multiples studies have established that high post-vaccination hemagglutination inhibition antibody titers develop in the majority of vaccinated children and young adults. These antibodies are protective against illness caused by strains that are antigenically similar to those strains of the same type or subtype included in the vaccine.

Dosage recommendations vary according to age group. Among previously unvaccinated children aged 6 months up to 9 years, two doses of inactivated vaccine administered >1 month apart are recommended for eliciting satisfactory antibody responses. If possible, the second dose should be administered before the onset of influenza season.

If a child aged 6 months up to 9 years receiving influenza vaccine for the first time does not receive a second dose of vaccine within the same season, only one dose of vaccine should be administered the following season; two doses are not required at that time. The CDC's Advisory Committee on Immunization Practices (ACIP) does not recommend that a child receiving influenza vaccine for the first time be administered the first dose of vaccine in the spring as a priming dose for the following season.

Among adults, studies have indicated limited or no improvement in antibody response when a second dose is administered during the same season. Even when the current influenza vaccine contains one or more antigens administered in previous years, annual vaccination is necessary because immunity declines during the year after vaccination. Vaccine prepared for a previous influenza season should not be administered to provide protection for the current season.

Children under 6 months of age usually acquire protective levels of anti-influenza antibody against specific influenza virus strains after vaccination, although the antibody response among children at high risk for complications might be lower than among healthy children. Two studies have documented that TIV vaccine decreases the incidence of influenza-associated otitis media among young children by approximately 30%.

Effectiveness of LAIV

The immunity provided by LAIV has been assessed in multiple studies. The LAIV virus strains replicate primarily in the cells of the nasopharynx. Its protective mechanisms are not completely understood but they appear to involve antibodies in both serum and nasal secretions. In studies, LAIV demonstrated up to 92% efficacy in preventing influenza in healthy children. It was also associated with reductions in otitis media (ear infections).

In a controlled study of both LAIV and TIV among 92 healthy adults, the overall efficacy against all three influenza strains combined was between 85% and 71%. The difference between the two vaccines was not statistically significant.

Multiple studies have demonstrated the ability of LAIV to stimulate an immune response (immunogenicity). LAIV is an option for vaccination of healthy, nonpregnant individuals aged 5 to 49 years who want to avoid influenza, and those who might be in close contact with others at high risk for severe complications, including healthcare workers.

LAIV can be administered to clients with minor acute illnesses (eg, diarrhea or mild upper respiratory tract infection with or without fever). However, if clinical judgment indicates nasal congestion is present that might impede delivery of the vaccine to the nasopharyngeal mucosa, deferral of administration should be considered until resolution of the illness.

Limited information is available regarding the frequency and severity of influenza illness or the benefits of influenza vaccination among people with HIV infection. However, reports indicate that influenza symptoms might be prolonged and the risk for complications from influenza increased for certain HIV-infected people. Because influenza can result in serious illness, vaccination is recommended for HIV-infected people, including HIV-infected pregnant women.

Whether concurrent administration of LAIV with other vaccines affects the safety or efficacy of either LAIV or the simultaneously administered vaccine is unknown. In the absence of specific data indicating interference, following the ACIP general recommendations for immunization is prudent. Inactivated vaccines do not interfere with the immune response to other inactivated vaccines or to live vaccines. Inactivated or live vaccines can be administered simultaneously with LAIV. However, after administration of a live vaccine, at least four weeks should pass before another live vaccine is administered.

The following populations should not be vaccinated with LAIV:

• People under 5 years or over 50 years of age
• People with asthma, reactive airways disease, or other chronic disorders of the pulmonary or cardiovascular systems; people with other underlying medical conditions, including such metabolic diseases as diabetes, renal dysfunction, and hemoglobinopathies; or people with known or suspected immunodeficiency diseases or who are receiving immunosuppressive therapies
• Children or adolescents receiving aspirin or other salicylates (because of the association of Reye syndrome with wild-type influenza virus infection);
• People with a history of group-B strep (GBS)
• Pregnant women
• People with a history of hypersensitivity, including anaphylaxis, to any of the components of LAIV or to eggs

The safety and effectiveness of LAIV co-administration with influenza antiviral medications has not been studied. However, because these antivirals reduce replication of influenza viruses, LAIV should not be administered until 48 hours after cessation of influenza antivirals, and influenza antiviral medications should not be administered for two weeks after receipt of LAIV.

LAIV must be stored at -15°C or colder in a frost-free freezer; a freezer box is no longer required. It can be thawed in a refrigerator and stored at 2°C to 8°C for up to 60 hours before use. It should not be refrozen after thawing because its potency could be decreased.

VACCINATION PROTOCOLS

Vaccination efficacy depends primarily on the age and the immune system of the recipient, on whether the viruses in the vaccine match those in circulation, and on the outcome being measured. Individuals with moderate-to-severe febrile illness usually should not be vaccinated until their symptoms abate. However, minor illnesses with or without fever do not contraindicate use of influenza vaccine, particularly among children with mild upper-respiratory tract infection or allergic rhinitis.

Vaccine effectiveness is lower among previously unvaccinated children under 9 years of age if they have received only one dose of vaccine, compared with children who have received two doses. All children aged 6 months up to 9 years who have never been vaccinated with either LAIV or TIV should receive two doses of vaccine. Children in this age range who receive TIV should have a booster dose of TIV administered at least 1 month after the initial dose and before the onset of influenza season, if possible.

LAIV is to be used only as a nasal spray and should not be administered by the intramuscular, intradermal, or intravenous route. It must be thawed before administration. This can be accomplished by holding an individual sprayer in the palm of the hand until thawed and then administering it immediately. Alternately, the vaccine can be thawed in a refrigerator and stored at 2°C to 8°C for up to 60 hours before use. Vaccine should not be refrozen after thawing.

LAIV is supplied in a pre-filled single-use sprayer containing 0.5 mL of vaccine. Approximately 0.25 mL (half of the sprayer contents) is sprayed into the first nostril with the recipient in upright position. An attached dose-divider clip is removed from the sprayer to administer the second half of the dose into the other nostril. Even if the vaccine recipient sneezes after administration, the dose should not be repeated.

LAIV should be administered annually according to the following schedule:

• Children aged 5 up to 9 years previously unvaccinated at any time with either LAIV or TIV should receive two dosesof LAIV separated by 6 to 10 weeks; if possible, the second dose of vaccine should be administered before the onset of influenza season.
• Children aged 5 up to 9 years previously vaccinated with either LAIV or TIV should receive one dose of LAIV. They do not require a second dose.
• Individuals aged 9 to 49 years should receive one dose of LAIV.

During periods when inactivated vaccine is in short supply, use of LAIV is encouraged when feasible for those eligible (including healthcare workers) in hopes of increasing availability of TIV for individuals in high-risk groups. Possible advantages of LAIV include its potential to induce a broad mucosal and systemic immune response, its ease of administration, and the general preference of nasal spray over injection.

Vaccine shortages do occur. The populations listed below have highest priority when they do; they are considered to be of equal importance:

• All children 6 to 23 months
• Healthy children aged 24 to 59 months and their household contacts and out-of-home caregivers
• Adults 65 years and older
• Individuals 2 to 64 years with underlying chronic medical conditions
• All women who will be pregnant during the influenza season
• Residents of nursing homes and long-term care facilities
• Children ages 6 months to 18 years on chronic aspirin therapy
• Healthcare workers involved in direct client care
• Out-of-home caregivers and household contacts of children of ages under 6 months

The ACIP emphasizes that influenza vaccine should continue to be offered throughout the influenza season even after influenza has been documented in a community.

Contraindications for Influenza Vaccine

Individuals in the following groups should not receive influenza vaccine before talking with their doctor:

• Those with a severe allergy (ie, anaphylactic allergic reaction) to hens' eggs
• People who had onset of Guillain-Barré syndrome during the 6 weeks after receiving influenza vaccine

USING ANTIVIRAL AGENTS FOR INFLUENZA

Antiviral drugs for influenza are an adjunct to influenza vaccine for controlling and preventing influenza. These agents are not a substitute for vaccination. Four licensed influenza antiviral agents are available in the United States: amantadine, rimantadine, zanamivir, and oseltamivir.

Currently, neither amantadine nor rimantadine are recommended for the treatment or prevention of influenza A in the United States because recent data indicate widespread resistance of influenza virus to these medications. Until susceptibility to adamantanes has been re-established among circulating influenza A viruses, oseltamivir or zanamivir may be prescribed if an antiviral is indicated.

Zanamivir and oseltamivir are chemically related antiviral drugs known as neuraminidase inhibitors that have activity against both influenza A and B viruses. Both zanamivir and oseltamivir were approved in 1999 for treating uncomplicated influenza infections. Zanamivir is approved for treating individuals over 7 years old, and oseltamivir is approved for treatment for those over 1 year old. In 2000 oseltamivir was approved for chemoprophylaxis of influenza among individuals over 13 years old.

INFECTION CONTROL MEASURES

The flu spreads in respiratory droplets from coughing and sneezing. It usually spreads from person to person, though occasionally people may become infected if they touch the mouth and nose after touching something with virus particles on it.

A combination of infection control strategies is recommended to decrease transmission of influenza in healthcare settings. These include influenza immunization for people at high risk for complications, immunization for healthcare workers, respiratory hygiene/cough etiquette, Standard Precautions and droplet precautions, and visitor and worker restrictions programs. Influenza clients should be given private rooms when possible and healthcare personnel should be encouraged to wear masks for close client contact (within 3 feet), and gowns and gloves if contact with respiratory secretions is likely.

The use of surgical or procedure masks by infectious clients may help contain their respiratory secretions and limit exposure to others. When a client is not wearing a mask (eg, in an isolation room), having healthcare personnel mask for close contact with the client may prevent nose and mouth contact with respiratory droplets. However, no studies have definitively shown that mask use by either infectious clients or healthcare personnel prevents influenza transmission.

In the United States, disposable surgical and procedure masks have been used widely in healthcare settings to prevent exposure to respiratory infections, but they have not been used commonly in community settings, such as schools or businesses, or at public gatherings.

CONCLUSION

Vaccination is the primary method for preventing influenza and its secondary complications. The introduction of live attenuated influenza vaccine (LAIV) administered intranasally is simplifying delivery of this crucial medication to a large segment of the population. Administration of antiviral medications, either for the early treatment of influenza infection or for prophylaxis, is a useful adjunct in the control of influenza.

Posted April 16, 2007

Expires May 1, 2009

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