Description

Influenza is caused by infection with influenza virus. Human influenza viruses can be divided into two types: A and B. Influenza A viruses are further classified into subtypes on the basis of two surface proteins: hemagglutinin (H) and neuraminidase (N). Both influenza A and B viruses undergo continual minor antigenic change (i.e., drift), but influenza B viruses evolve more slowly and are not divided into subtypes. Only influenza A viruses can undergo the major antigenic changes (i.e., shift) so that the H or both the H and N are replaced and a new influenza A virus with pandemic potential can result.

A (H3N2), and influenza B viruses currently circulate globally among humans.

Occurrence

In temperate climates, seasonal epidemics of influenza generally occur during the winter months on an annual or near-annual basis. In the United States, annual epidemics are responsible for an average of approximately 36,000 deaths. 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 persons older than 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 cardio-pulmonary disease). Children younger than 2 years of age have rates of influenza-related hospitalization as high as those in the elderly. The emergence of a novel human influenza A virus could lead to a global pandemic, during which rates of morbidity and mortality from influenza-related complications could increase dramatically (1).

The public health threat of a pandemic arising from novel influenza subtypes, including influenza A (H5N1), becomes imminent only if the virus gains the ability to spread efficiently from one human to another. Such transmission has not yet been observed with the currently circulating A (H5N1) viruses. However, a few cases of limited person-to-person spread of H5N1 viruses have been reported as of 2006, and no instances of transmission continuing beyond one person are thought to have occurred (for current information see http://www.cdc.gov/flu/avian/ gen-info/avian-flu-humans.htm). Since human infections with avian H5N1 viruses were first documented in 1997, no sustained human-to-human transmission has been documented. However, because influenza A viruses have the ability to constantly undergo change and may gain the ability to spread easily between people, monitoring for human infection and person-to-person transmission is an important component of pandemic preparedness (2).

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 (1). 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 (3). Although human infections with H5N1 viruses are rare, CDC advises travelers to countries with known outbreaks of H5N1 to avoid poultry farms, contact with sick or dead poultry, as well as with poultry that have no apparent symptoms, surfaces that may have been contaminated by poultry feces or secretions, and animals in live-food markets. Since transmission of H5N1 viruses to two persons through consumption of uncooked duck blood may also have occurred in Vietnam in 2005, uncooked poultry or poultry products, including blood, should not be consumed. For more information, see http://wwwn.cdc.gov/travel/contentAvianFluAsia.aspx.

Because the situation is evolving, travelers can stay abreast of new developments by checking the official U.S. government website for pandemic flu (http://www.pandemicflu.gov/). The CDC Travelers’ Health website (http://wwwn.cdc.gov/travel/contentAvianFluInformation.aspx), CDC Avian Influenza website (http://www.cdc.gov/flu/avian/), and the WHO website (http://www.who.int/csr/disease/avian_influenza/en/index.html) are also regularly updated.

Clinical Presentation

Uncomplicated influenza illness is characterized by the abrupt onset of constitutional and respiratory signs and symptoms (e.g., 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, and laboratory testing can aid in diagnosis. Influenza illness typically resolves relatively quickly for most persons, although cough and malaise can persist for longer than 2 weeks. Influenza can exacerbate chronic conditions (e.g., pulmonary or cardiac disease), and/or lead to secondary infections. Influenza-related deaths can result from pneumonia, as well as from exacerbations of cardiopulmonary conditions and other chronic diseases (1). H5N1 infections in humans, although rare, can cause death or serious disease (for more information see the World Health Organization’s Avian Influenza Fact Sheet at ttp://www.who.int/mediacentre/factsheets/avian_influenza/en/index.html#humans).

Prevention

Handwashing and cough hygiene can play important roles in limiting person–to-person transmission of influenza. Where handwashing is not available, use of hand gels containing greater than 60% alcohol may be used (see Chapter 2 and ACIP recommendations (http://www.cdc.gov/nip/publications/acip-list.htm) [1]). Avoiding travel when ill will also help to limit transmission.

VACCINES

Annual vaccination of persons at high risk for complications and vaccination of health-care workers and close contacts of high risk persons before the influenza season is the most effective measure for preventing influenza and associated complications. The influenza vaccine must be administered yearly to optimize protection because vaccine-derived immunity declines over time and because the vaccine strains are updated annually to reflect ongoing antigenic changes among circulating influenza viruses. 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 take place by spring when possible, because influenza vaccine may 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 (1).

Two types of influenza vaccine are currently available for use in the United States: inactivated vaccine, administered by intramuscular injection, and live, attenuated influenza vaccine (LAIV), administered by nasal spray. LAIV is currently approved for use only in healthy persons 2-49 years of age who are not pregnant  (Updated October 17, 2008) (5).

A vaccine to protect humans against influenza A (H5N1) is not yet available commercially, but candidate vaccines are undergoing human clinical trials in the United States.

For inactivated vaccine, two doses administered at least 1 month apart are required for previously unvaccinated infants and children younger than 9 years of age. For previously unvaccinated children aged 5-8 years receiving LAIV, two doses are administered at least 6 weeks apart. For situations in which a child receives two different vaccine types, 4 weeks should separate doses if inactivated vaccine is used first, and 6 weeks should separate doses if LAIV is used first.

Composition of the Vaccines

Both influenza vaccines contain three strains of inactivated influenza viruses and do not cause influenza. The viruses used in both vaccines are representative of viruses likely to circulate in the upcoming season, and usually one or more vaccine strains are updated annually. Influenza vaccine distributed in the United States may also contain thimerosal, a mercury-containing preservative.

Adverse Reactions

Inactivated Vaccine

The most frequent side effect of vaccination with inactivated vaccine is soreness and redness 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. 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 (e.g., young children). These reactions begin 6-12 hours after vaccination and can persist for 1-2 days

LAIV

The most frequent side effects of vaccination with LAIV include nasal congestion, headache, fever, vomiting, abdominal pain, and myalgia. These symptoms are associated more often with the first dose and are self-limited. There may be an increase in asthma or reactive airway disease in children younger than 5 years of age, and LAIV is not approved for use among children in this age group.

Other Reactions

Allergic

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 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 consult a physician for appropriate evaluation to determine if vaccine should be administered. People who have documented immune globulin E (IgE)-mediated hypersensitivity to eggs, including those who have had occupational asthma or other allergic responses due to exposure to egg protein, may 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 (1).

Guillain-Barré Syndrome (GBS)

No substantial increase in GBS has been associated with influenza vaccines except with the “swine flu” vaccine of 1976. A study of the 1992-93 and 1993-94 influenza seasons estimated a possible risk of GBS of slightly more than 1 case per million people vaccinated. The potential benefits of influenza vaccination in preventing serious illness, hospitalization, and death greatly outweigh the possible risks for developing vaccine-associated GBS (1).

Precautions and Contraindications

Pregnancy

Influenza vaccination with inactivated vaccine is considered safe and is recommended during any stage of pregnancy (1). Breastfeeding does not adversely affect immune response and is not a contraindication for vaccination.

Persons Infected with HIV

The risk for influenza-related death among persons with AIDS appears higher than among those without AIDS. 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 (1).

Treatment

ANTIVIRAL MEDICATIONS

Influenza-specific antiviral drugs for chemoprophylaxis of influenza are important adjuncts to vaccine. The four currently licensed U.S. antiviral agents are amantadine, rimantadine, zanamivir, and oseltamivir; amantadine and rimantadine have a mechanism of action effective only against influenza A viruses, while the neuraminidase inhibitors oseltamivir and zanamivir are effective against both influenza A and B viruses. On the basis of antiviral drug testing results conducted at CDC and in Canada indicating high levels of resistance among influenza A viruses, CDC recommends that neither amantadine nor rimantadine be used for the treatment or chemoprophylaxis of influenza A in the United States until susceptibility to these antiviral medications has been re-established among circulating influenza A viruses (1,4).

Oseltamivir or zanamivir can be prescribed if antiviral treatment of influenza is indicated. Oseltamivir is approved for treatment of persons aged 1 year or older, and zanamivir is approved for treatment of persons aged 7 years or older. Oseltamivir and zanamivir can be used for chemoprophylaxis of influenza; oseltamivir is licensed for use in persons aged 1 year or older, and zanamivir is licensed for used in persons at least 5 years of age (1). These two drugs differ in dosing, approved age groups for use, side effects, and cost.

Some H5N1 viruses currently infecting birds and humans are resistant to amantadine and rimantadine, two antiviral medications commonly used to treat influenza. Most of the H5N1 viruses tested have been susceptible to the antiviral medications oseltamivir (Tamiflu) and zanamivir (Relenza), but resistance has been reported. The effectiveness of antivirals for treating H5N1 virus infections is unknown. For more information about influenza antiviral drugs, see http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm#antiviral.

References

1. Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR10):1-42.
2. CDC. Avian Influenza Infection in Humans. 2006 [accessed 2006 October]; Available from: http://www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm.
3. Uyeki T, Zane SB, Bodnar UR, Fielding KL, Buxton JA, Miller JM, et al.; Alaska/Yukon Territory Respiratory Outbreak Investigation Team. Large summertime influenza A outbreak among tourists in Alaska and the Yukon Territory. Clin Infect Dis. 2003;36:1095-102.
4. Bright RS, Shay DK, Shu B, Cox NJ, Klimov AI. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States. JAMA. 2006;95:891-4.
5. Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. 2008;57(RR07):1-60.