Influenza

Description

Influenza is caused by infection with either influenza A or B viruses. Influenza A viruses are further classified into subtypes on the basis of two surface antigens: hemagglutinin (H) and neuraminidase (N). Although both influenza A and B viruses undergo continual minor antigenic change (i.e., drift), influenza B viruses evolve more slowly and are not divided into subtypes. Since 1977, influenza A (H1N1), A (H3N2), and influenza B viruses have been in global circulation. Since 2001, influenza A (H1N2) viruses have been isolated from several countries in North America, Europe, and Asia. However, whether there will be long-term widespread circulation of this virus subtype, which is a result of genetic reassortment between currently circulating A (H1N1) and A (H3N2) viruses, is uncertain.

Occurrence

In recent studies, influenza infection among travelers is quite common; hence, it may rank with hepatitis A as one of the most common vaccine-preventable diseases of travelers. Seasonal epidemics of influenza generally occur during the winter months on an annual or near annual basis and are responsible for an average of approximately 20,000 deaths in the United States each year. Influenza virus infections cause disease in all age groups. Rates of infection are highest among infants, children, and adolescents, but rates of serious illness and death are highest among persons >65 years of age and persons of any age who have medical conditions that place them at high risk for complications from influenza (e.g., chronic cardiopulmonary disease). The emergence of a novel human influenza A virus can lead to a global pandemic, during which rates of morbidity and mortality from influenza-related complications can increase dramatically.

Risk for Travelers

The risk for exposure to influenza during international travel depends on the time of year and destination. In the tropics, influenza can occur throughout the year, while in the temperate regions of the Southern Hemisphere most activity occurs from April through September. In temperate climates, travelers can also be exposed to influenza during the summer, especially when traveling as part of large tourist groups with travelers from areas of the world where influenza viruses are circulating. Influenza vaccine should be recommended before travel for persons at high risk for complications of influenza if 1) influenza vaccine was not received during the preceding fall or winter, 2) travel is planned to the tropics, 3) travel is planned with large groups of tourists at any time of year, or 4) travel is planned to the Southern Hemisphere from April through September. In North America, travel-related influenza vaccination should be administered by spring when possible, because influenza vaccine might not be available during the summer. Travelers at high risk for influenza-related complications who plan summer travel should consult with their physicians to discuss the symptoms and risks of influenza before embarking.

Prevention

Vaccine

In the United States, the main option for reducing the impact of influenza is immunoprophylaxis with inactivated vaccine. Annual vaccination of persons at high risk for complications before the influenza season is the most effective measure for preventing influenza and associated complications. Annual influenza vaccination is recommended for the following groups who are at risk for complications from influenza:

• Persons >65 years of age.
• Residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions.
• Anyone >6 months of age who has chronic disorders of the pulmonary or cardiovascular systems, including asthma.
• Anyone >6 months of age who has required regular medical follow-up or hospitalization during the preceding year because of a chronic metabolic disease (including diabetes mellitus), renal dysfunction, hemoglobinopathy, or immunosuppression (including immunosuppression caused by medication and HIV).
• Anyone 6 months to 18 years of age who is receiving long-term aspirin therapy and might be at risk for developing Reye syndrome after influenza.
• Women who will be in the second or third trimester of pregnancy during the influenza season.
• Health-care workers and others (including household members) in close contact with persons at high risk for influenza-related complications.

Vaccination is also recommended for persons 50–64 years of age because a substantial proportion of these persons may have a medical condition that places them at increased risk for influenza-related complications. Vaccination is encouraged for healthy children 6–23 months of age since this population is at increased risk for influenza-related hospitalization.

Dosing, Route, and Timing of Vaccination

For persons at high risk for complications from influenza, annual vaccination is recommended because vaccine-derived immunity declines during the year and because the vaccine strains are continually updated to reflect ongoing antigenic changes among circulating influenza viruses. Dosage recommendations differ according to age group. Two doses administered at least 1 month apart are required for previously unvaccinated infants and children <9 years of age. In adults, studies have indicated little or no improvement in antibody response when a second dose is administered during the same season, and therefore a booster is not recommended.

The intramuscular route is recommended for influenza vaccine. Infants and young children should be vaccinated in the anterolateral aspect of the thigh; all other vaccine recipients should be vaccinated in the deltoid muscle.

Composition of the Vaccine

Influenza vaccine contains three strains of inactivated influenza viruses. These viruses are representative of viruses likely to circulate in the upcoming season, and usually one or more vaccine strains are updated annually. Because the vaccine is grown in hen eggs, the vaccine might contain small amounts of egg protein. Influenza vaccine distributed in the United States might also contain thimerosal, a mercury-containing preservative. The package insert should be consulted regarding the use of other compounds to inactivate the viruses or limit bacterial contamination.

Adverse Reactions

Inactivated influenza vaccine contains viral proteins but no live virus and cannot cause influenza. Respiratory disease after vaccination represents coincidental illness unrelated to influenza vaccination.

Local Reactions. The most frequent side effect of vaccination is soreness at the vaccination site that lasts up to 2 days. These local reactions generally are mild and rarely interfere with the ability to conduct usual daily activities.

Systemic Reactions. Fever, malaise, myalgia, and other systemic symptoms can occur following vaccination and most often affect persons who have had no previous exposure to the influenza virus antigens in the vaccine (e.g., young children). These reactions begin 6–12 hours after vaccination and can persist for 1–2 days.

Immediate reactions (e.g., hives, angioedema, allergic asthma, and systemic anaphylaxis) rarely occur after influenza vaccination. These reactions probably result from hypersensitivity to some vaccine component; most reactions likely are caused by residual egg protein and occur among persons who have severe egg allergy. Persons who have developed hives, have had swelling of the lips or tongue, or have experienced acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation to determine if vaccine should be administered. Persons who have documented immunoglobulin E (IgE)-mediated hyper-sensitivity to eggs, including those who have had occupational asthma or other allergic responses due to exposure to egg protein, might also be at increased risk for reactions from influenza vaccine, and similar consultation should be advised. Protocols have been published for safely administering influenza vaccine to persons with egg allergies.

Guillain-Barré Syndrome (GBS). Investigations to date indicate no substantial increase in GBS associated with influenza vaccines (other than the “swine flu” vaccine of 1976). A study of the 1992-93 and 1993-94 influenza seasons estimated a risk of GBS of slightly more than 1 case per million persons vaccinated. The potential benefits of influenza vaccination in preventing serious illness, hospitalization, and death greatly outweigh the possible risks for developing vaccine-associated GBS.

Precautions and Contraindications

The target groups for influenza and pneumococcal vaccination overlap considerably. For travelers at high risk who have not previously been vaccinated with pneumococcal vaccine, health-care providers should strongly consider administering pneumococcal and influenza vaccines concurrently. Both vaccines can be administered at the same time at different sites without increasing side effects. Infants and children at high risk for influenza-related complications can receive influenza vaccine at the same time they receive other routine vaccinations.

Pregnancy. Because currently available influenza vaccine is inactivated, many experts consider influenza vaccination safe during any stage of pregnancy. A study of influenza vaccination of >2,000 pregnant women demonstrated no adverse fetal effects associated with influenza vaccine. However, more data are needed. Some experts prefer to administer influenza vaccine during the second trimester to avoid a coincidental association with spontaneous abortion, which is common in the first trimester, and because exposures to vaccines have traditionally been avoided during the first trimester. Influenza vaccine does not affect the safety of mothers who are breast-feeding or their infants. Breast-feeding does not adversely affect immune response and is not a contraindication for vaccination.

Persons Infected with HIV. Information is limited on the frequency and severity of influenza illness or the benefits of influenza vaccination for HIV-infected persons. On the basis of a recent risk-modeling study, the risk for influenza-related death in persons with AIDS appears higher than in those without AIDS. In addition, the symptoms of influenza might be prolonged and the risk for complications from influenza increased for certain HIV-infected persons. HIV-infected persons who have minimal AIDS-related symptoms and high CD4+ T-lymphocyte cell counts can develop protective influenza antibody titers from influenza vaccine, and vaccination has been shown to prevent influenza in this group. However, influenza vaccine might not induce protective antibody titers in persons who have advanced HIV disease and low CD4+ T-lymphocyte cell counts; a second dose of vaccine does not improve the immune response in these persons. Deterioration of CD4+ T-lymphocyte cell counts and progression of HIV disease have not been demonstrated in HIV-infected persons who receive the vaccine. The effect of antiretroviral therapy on potential increases in HIV ribonucleic acid (RNA) levels following either natural influenza infection or influenza vaccine is unknown. Because influenza can result in serious illness and complications and because influenza vaccination can result in the production of protective antibody titers, vaccination will benefit many HIV-infected persons, including HIV-infected pregnant women.

Other

Influenza-specific antiviral drugs for chemoprophylaxis and therapy of influenza are important adjuncts to vaccine. The four currently licensed U.S. antiviral agents are amantadine, rimantadine, zanamivir, and oseltamivir. Amantadine and rimantadine are active against influenza A viruses but not influenza B viruses. Both drugs are approved by the U.S. Food and Drug Administration for the treatment and prophylaxis of influenza A virus infections. Zanamivir and oseltamivir have activity against both influenza A and B viruses. Both drugs are currently approved for treatment, but only oseltamivir has been approved for prophylaxis. These four drugs differ in terms of dosing, approved age groups for use, side effects, and cost. Amantadine and rimantadine are approved for prophylaxis in persons >1 year of age, and oseltamivir is approved for prophylaxis in persons >13 years of age. The package inserts should be consulted for more information.

For more information about influenza, see the CDC Influenza site at http://www.cdc.gov/flu.

— Scott Harper