The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has released recommendations for the prevention and control of influenza during the 1999–2000 influenza season. The liaison representative to ACIP from the American Academy of Family Physicians is Richard Zimmerman, M.D., M.P.H., University of Pittsburgh School of Medicine, Pittsburgh, Pa.

The recommendations cover the following areas: options for the control of influenza; inactivated vaccine for influenza A and B; use of the influenza vaccine; target groups for vaccination; vaccination of other groups; persons who should not be vaccinated; administration of influenza vaccine; side effects and adverse reactions; simultaneous administration of other vaccines; timing of influenza vaccination; strategies for implementing influenza vaccine recommendations; antiviral agents for influenza A; indications for use of amantadine and rimantadine; considerations for selecting amantadine and rimantadine; and considerations for selecting these agents for chemoprophylaxis or treatment. The recommendations also contain sources of information on influenza-control programs and a selected reference list.

The principle changes in this year's recommendations include information on the influenza virus strains covered by the 1999–2000 trivalent vaccine; discussion of the potential expanded use of influenza vaccine; new background information on live-attenuated influenza vaccines, neuraminidase-inhibitor drugs and rapid diagnostic tests; new information on the epidemiology of influenza among travelers; and the addition of reference citations.

The complete report of the ACIP recommendations is published in Morbidity and Mortality Weekly Report recommendations and reports series (MMWR Morb Mortal Wkly Rep 1999;48[RR-4]:1–28). It can also be accessed at the Web site of the Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC at http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm.

The 1999–2000 Influenza Vaccine

The trivalent vaccine for the 1999–2000 influenza season includes A/Beijing/262/95-like (H1N1), A/Sydney/5/97-like (H3N2) and B/Beijing/184/93-like hemagglutinin antigens. For the B/Beijing/184/93-like antigen, U.S. manufacturers will use the antigenically equivalent B/Yamanashi/166/98 virus because of its growth properties and because it is representative of currently circulating B viruses.

ACIP recommends influenza vaccine for any person six months old or over who is at increased risk for complications of influenza. Health care workers and others in close contact with persons in high-risk groups should be vaccinated. ACIP recommends that anyone who would like to reduce the risk of contacting the influenza virus should be vaccinated.

Target Groups

Groups at high risk for influenza-related complications include (1) persons 65 years of age and older; (2) residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions; (3) adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including asthma; (4) adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases, renal dysfunction, hemoglobinopathies or immunosuppression; (5) children and teenagers (six months to 18 years of age) who are receiving long-term aspirin therapy and therefore might be at risk for developing Reye's syndrome after influenza; and (6) women who will be in the second or third trimester of pregnancy during the influenza season.

Other Groups to Consider

• Persons Infected with Human Immunodeficiency Virus (HIV). Some reports suggest that symptoms might be prolonged and the risk for complications increased in some persons with HIV infection. Influenza vaccine has produced substantial antibody titers against influenza in vaccinated HIV-infected persons who have minimal acquired immunodeficiency syndrome-related symptoms and high CD4 cell counts. In patients who have advanced HIV disease and low CD4 cell counts, however, influenza vaccine might not induce protective antibody titers; a second dose of vaccine does not improve the immune response in these persons.

• Breast-feeding Mothers. Influenza vaccine does not affect the safety of breast-feeding for mothers or their infants. Breast feeding is not a contraindication for vaccination.

• Travelers. Persons at high risk should consider receiving influenza vaccine before travel if they were not vaccinated with the vaccine during the preceding fall or winter and they plan to (1) travel to the tropics; (2) travel with large organized tourist groups at any time of the year; or (3) travel to the southern hemisphere from April through September. Persons in high-risk groups should be encouraged to receive the current vaccine.

Before traveling during the summer in North America, persons older than 65 years and others at high risk should consult their physician about carrying antiviral medications for either prophylaxis or treatment for influenza if the influenza vaccine is not available during the summer.

• General Population. Anyone who wants to reduce their likelihood of contracting influenza should receive the vaccine. Those who provide community services should be considered for vaccination to minimize disruption of essential activities during outbreaks of influenza. Students and other persons in institutional settings should be encouraged to receive the vaccine. The vaccine can be given to children as young as six months.

Persons Who Should Not Be Vaccinated

Inactivated influenza vaccine should not be given to persons known to have anaphylactic hypersensitivity to eggs or to other components of the influenza vaccine without first consulting a physician. Use of an antiviral agent is an option for preventing influenza A in such persons. However, persons who have a history of anaphylactic hypersensitivity to vaccine components but who are also at high risk for complications of influenza can benefit from vaccine after appropriate allergy evaluation and desensitization.

Adults with an illness accompanied by fever usually should not be vaccinated until their symptoms have abated. However, adults and children with minor illnesses with or without fever can receive the vaccine, particularly children with mild upper respiratory tract infection or allergic rhinitis.

Side Effects and Adverse Reactions

Physicians should assure their patients that the influenza vaccine does not cause influenza and that respiratory disease after vaccination is coincidental and not related to the vaccination. Soreness at the vaccination site is the most common side effect. It occurs in 10 to 64 percent of patients, may last up to two days and generally is mild. The following types of systemic reactions have occurred:

• Fever, malaise, myalgia and other systemic symptoms can occur and most often affect persons who have had no previous exposure to the influenza virus antigens in the vaccine. These reactions may last up to two days.

• Allergic reactions, such as hives, allergic asthma and systemic anaphylaxis, rarely occur after vaccination. They probably result from hypersensitivity to some vaccine component; most allergic reactions are caused by residual egg protein. Persons who have developed hives, have had swelling of the lips or tongue, or have had acute respiratory distress or collapse after eating eggs should consult a physician for appropriate evaluation before deciding whether to receive the vaccine. Persons who have documented IgE-mediated hypersensitivity to eggs might also be at increased risk for reactions from influenza vaccine, and similar consultation should be considered.

Although the 1976 swine influenza vaccine was associated with an increased incidence of Guillain-Barré syndrome (GBS), evidence for a causal relationship with subsequent vaccines is less clear. During three of four influenza seasons studied from 1977 to 1991, the overall relative risk for GBS after vaccination was slightly increased but was not statistically significant in any of these studies. In a more recent study, investigators found an elevation in the overall relative risk for GBS during the six weeks following vaccination. The possibility exists that these increases in incidence in GBS may be caused by other factors. According to ACIP, the potential benefits of influenza vaccination clearly outweigh the possible risks for vaccine-associated GBS. The average case-fatality ratio for GBS is 6 percent and increases with age. However, no evidence indicates that the case-fatality ratio for GBS differs among vaccinated persons and those not vaccinated.

Timing of the Vaccine

Beginning each September, persons at high risk who are seen for routine health care or as a result of hospitalization should be offered the influenza vaccine. Opportunities to vaccinate persons at high risk for complications of influenza should not be missed.

In the United States, influenza activity generally peaks between late December and early March. High levels of influenza activity infrequently occur before December in the contiguous 48 states. The vaccine should not be given too far in advance.

Dosing recommendations vary according to age group. According to ACIP, two doses given at least one month apart may be required for satisfactory antibody responses among previously unvaccinated children under nine years of age. If possible, the second dose should be administered before December. In adults, only one dose is necessary during each influenza season. Adults and older children should be vaccinated in the deltoid muscle, and infants and young children should be vaccinated in the anterolateral aspect of the thigh.

Potential New Vaccines

Intranasally administered, cold-adapted, live, attenuated, influenza virus vaccines are under development in the United States. The viruses in these vaccines replicate in the upper respiratory tract and elicit a specific protective immune response. Potential advantages of this type of vaccine include their ability to induce a broad mucosal and systemic immune response, ease of administration and the acceptability of an intranasal route of administration.

Potential Expansion of Groups Recommended for Vaccination

ACIP has formed a working group to look into issues related to the potential expansion of recommendations for the use of influenza vaccine. These include recommendations to consider young children under five years of age and persons 50 to 64 years of age as being at high risk for complications from influenza. Further studies are needed before ACIP will recommend routine vaccination of these two groups.

Antiviral Agents for Influenza A

Amantadine and rimantadine are indicated for the prophylaxis and treatment of influenza A infection. When administered prophylactically to healthy adults or children, both drugs are approximately 70 to 90 percent effective in preventing illness from influenza A infection. Because antiviral agents taken prophylactically can prevent illness but not subclinical infection, some persons who take these drugs can still develop immune responses to circulating influenza viruses.

When administered to healthy adults, amantadine and rimantadine can reduce the severity and duration of signs and symptoms of influenza A illness. There is limited information on the use of amantadine and rimantadine in the treatment of children with influenza A virus.

Use of Antiviral Agents as Prophylaxis

ACIP emphasizes that chemoprophylaxis is not a substitute for vaccination. Recommendations for chemoprophylaxis are provided to help clinicians make decisions regarding persons who are at greatest risk for severe illness and complications from influenza A virus infection. These groups of persons are as follows:

• Persons at high risk who are vaccinated after influenza activity has begun.

• Persons providing care to those at high risk.

• Persons who have immunodeficiency, including those with HIV infection.

• Persons who should not receive the influenza vaccine.

• Other persons, including those who do not want to contract influenza A illness.

Use of Antivirals as Therapy

Amantadine and rimantadine can reduce the severity and shorten the duration of influenza A illness in healthy adults when administered within 48 hours of illness onset. It is not known if antiviral therapy will prevent complications of influenza type A in persons at high risk. Rimantadine is approved only for prophylaxis in children, not for treatment in this age group. To reduce the emergence of antiviral drug-resistant viruses, treatment of persons who have influenza-like illness should be discontinued as soon as clinically warranted, generally after three to five days of treatment or within 24 to 48 hours after the disappearance of signs and symptoms.

Amantadine and rimantadine are administered orally. Both drugs are available in tablet or syrup form.

Side effects of both drugs are generally mild. Both amantadine and rimantadine can cause central nervous system and gastrointestinal side effects when administered to young, healthy adults at equivalent dosages of 200 mg per day. However, the incidence of central nervous system side effects is higher in persons taking amantadine than in those taking rimantadine. Gastrointestinal side effects occur in about 1 to 3 percent of persons taking either drug.

Sources of Information on Influenza

Information regarding influenza surveillance is available through the CDC Voice Information System at 888-232-3228; the CDC fax information service at 888-232-3299; or the Web site of the Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC at http://www.cdc.gov/ncidod/diseases/flu/fluvirus.htm. From October through May, the information is updated at least every other week. In addition, periodic updates about influenza are published in the weekly MMWR.