Influenza

Description

Influenzas A and B are the major types of influenza viruses that cause human respiratory disease. 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 antigenic change (that is, antigenic drift), influenza B viruses undergo antigenic change more slowly and are not divided into subtypes. Since 1977, influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation.

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Occurrence

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 morbidity and mortality are highest among people 50 years of age or older and people of any age who have medical conditions that place them at high risk for complications from influenza. Influenza viruses also can cause global epidemics of disease, known as pandemics, 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 varies depending on the time of year and destination. In the tropics, influenza can occur throughout the year, while most activity occurs from April through September in the temperate regions of the Southern Hemisphere. 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. Travelers at high risk for complications of influenza should be advised to consider receiving influenza vaccine before travel 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. Travelers at high risk who received the previous season's vaccine before travel should be revaccinated in the fall or winter with the current vaccine.

Because influenza vaccine might not be available during the summer in North America, travelers 50 years of age or older and others at high risk for influenza-related complications who plan summer travel might be advised to consult with their physicians to discuss the symptoms and risks of influenza before embarking on their travel.

Preventive Measures

Vaccine

In the United States, the main option for reducing the impact of influenza is immunoprophylaxis with inactivated (that is, killed-virus) vaccine. In addition, the use of influenza-specific antiviral drugs for chemoprophylaxis or therapy of influenza are important adjuncts to vaccine. Annual vaccination of people at high risk for complications before the influenza season is the most effective measure for reducing the impact. Vaccine is recommended for all travelers, and particularly for the following groups who are at risk for complications from influenza:

People 50 years of age or older. (In 2000, the 50- through 64-years-of-age group was added to those recommended for annual vaccination because a substantial proportion of them have a medical condition that places them at increased risk of influenza-related complications.)
Residents of nursing homes and other chronic-care facilities that house people of any age who have chronic medical conditions.
Anyone 6 months of age or older who has chronic disorders of the pulmonary or cardiovascular systems, including asthma.
Anyone 6 months of age or older who has required regular medical followup or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications, human immunodeficiency virus [HIV], or acquired immunodeficiency syndrome [AIDS]).
Anyone 6 months to 18 years of age who is receiving long-term aspirin therapy and, therefore, might be at risk for developing Reye's syndrome after influenza.
Women who will be in the second or third trimester of pregnancy during the influenza season.

Dosing, Route, and Timing of Vaccination

Even when current influenza vaccine contains one or more of the antigens administered in previous years, annual vaccination with the current vaccine is necessary because immunity declines during the year after vaccination. Dosage recommendations differ according to age group. Two doses administered at least one month apart may be required for satisfactory antibody responses among previously unvaccinated infants and children younger than 9 years of age. The second dose should be administered before December, if possible. In adults, studies have indicated little or no improvement in antibody response when a second dose is administered during the same season.

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 updated annually and are representative of viruses likely to circulate in the upcoming season. 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. Manufacturing processes differ by manufacturer and 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 noninfectious viruses 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 people who have had no previous exposure to the influenza virus antigens in the vaccine (for example, young children). These reactions begin 6 to 12 hours after vaccination and can persist for 1 to 2 days.

Immediate--presumably allergic--reactions (for example, 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 people who have severe egg allergy. People who have developed hives, have had swelling of the lips or tongue, or have experienced acute respiratory distress or collapse after eating eggs should be advised to consult a physician for appropriate evaluation to help determine if vaccine should be administered. People 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 people with egg allergies.

Guillain-Barré Syndrome (GBS).-- Investigations to date suggest that there is no large increase in GBS associated with influenza vaccines (other than the "swine flu" vaccine) and that if influenza vaccine does pose a risk it is probably quite small--on the order of 1 to 2 episodes per million people vaccinated. There are case reports of GBS following influenza, but no epidemiologic studies documenting such an association.

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. However, influenza vaccine is administered each year, while pneumococcal vaccine is not. 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 an inactivated vaccine, many experts consider influenza vaccination safe during any stage of pregnancy. A study of influenza vaccination of more than 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 this time. 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.

People Infected With Human Immunodeficiency Virus (HIV).-- Limited information exists regarding the frequency and severity of influenza illness or the benefits of influenza vaccination among HIV-infected people. Influenza vaccine has produced protective influenza antibody titers and has been shown to prevent influenza in HIV-infected people who have minimal AIDS-related symptoms and high CD4+ T-lymphocyte cell counts. However, in people who have advanced HIV disease and low CD4+ T-lymphocyte cell counts, influenza vaccine might not induce protective antibody titers; a second dose of vaccine does not improve the immune response in these people. Deterioration of CD4+ T-lymphocyte cell counts and progression of HIV disease have not been demonstrated among HIV-infected people 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 people, including HIV-infected pregnant women.

Other

Antiviral drugs for influenza are an important adjunct to influenza vaccine for the control and prevention of influenza. The four currently licensed U.S. agents are amantadine, rimantadine, zanamivir, and oseltamivir. Amantadine and rimantadine have specific activity against influenza A viruses but not influenza B viruses. Both 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 influenzas A and B. Both drugs are currently approved for treatment, though only oseltamivir has been approved for prophylaxis. These four drugs differ in terms of dosing, approved age groups for use, side effects, and cost. The package inserts should be consulted for more information.

Credits: National Center for Infectious Disease