The Advisory Committee on Immunization Practices (ACIP) has released recommendations for the prevention and control of influenza during the 1998–99 influenza season. The recommendations cover options for the control of influenza, inactivated vaccine for influenza A and B, use of the influenza vaccine, target groups for vaccination programs, vaccination of other groups, persons who should not be vaccinated, 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, 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 bibliography.

The principal changes in this year's recommendations include the following: information about the influenza virus strains included in the trivalent vaccine for 1998-99; more detailed information about influenza-associated rates of hospitalization; and updated information on the possible relationship between Guillain Barré syndrome (GBS) and influenza vaccination.

The complete report of the ACIP recommendations is published in Morbidity and Mortality Weekly Report recommendations and reports series (MMWR Morb Mortal Wkly Rep 47;[RR-6]:1–35). The following information has been excerpted from the report.

The 1998–99 Influenza Vaccine

The trivalent influenza vaccine prepared for the 1998–99 influenza season will include 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 strain B/Harbin/07/93 because of its growth properties. Annual vaccination with the current vaccine is necessary since immunity declines during the year following vaccination. Because the 1997–98 vaccine differs from the 1998–99 vaccine, it should not be given to provide protection for the 1998–99 influenza season.

According to ACIP, two doses administered at least one month apart may be required for satisfactory antibody responses among previously unvaccinated children under nine years of age. However, studies of vaccines similar to those being used currently have indicated little or no improvement in antibody response when a second dose is administered to adults during the same 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.

Target Groups

Organized vaccination programs should be available for persons at high risk for influenza and their close contacts. Groups at increased risk for influenza-related complications include (1) persons 65 years and older; (2) residents of nursing homes and other chronic-care facilities where persons of any age with chronic medical conditions reside; (3) adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including children with 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 (aged six months to 18 years) 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

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

• Breast-Feeding Mothers. Influenza vaccine does not affect the safety of breast-feeding for mothers or infants. Breast-feeding does not adversely affect immune response and is not a contraindication for vaccination.

• Persons Traveling to Foreign Countries. Persons who travel to the tropics at any time of year or to the Southern Hemisphere from April through September should consider vaccination before travel if they were not vaccinated the previous fall or winter. Persons in high-risk groups especially should be encouraged to receive the most current vaccine.

• General Population. Anyone who wants to reduce the likelihood of becoming ill with influenza should receive influenza vaccine. Persons who provide essential community services should be considered for vaccination to minimize disruption of essential activities during influenza outbreaks. Students or other persons in institutional settings should also receive the vaccine.

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 amantadine or rimantadine is an option for prevention of influenza A in these 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 acute febrile illness usually should not be vaccinated until their symptoms have abated. However, minor illnesses with or without fever should not contraindicate the use of influenza vaccine, particularly among children with mild upper respiratory tract infection or allergic rhinitis.

Side Effects and Adverse Reactions

Influenza vaccine cannot cause influenza. Respiratory disease after vaccination is coincidental and not related to the vaccination. Soreness at the vaccination site is the most common side effect. It may last up to two days. These local reactions are generally mild. The following two types of systemic reactions have occurred:

• Fever, malaise, myalgia and other systemic symptoms can occur following vaccination and most often affect persons who have had no exposure to the influenza virus antigens in the vaccine. These reactions begin six to 12 hours after vaccination and can last for one or two days.

• Immediate (presumably allergic) reactions rarely occur after influenza vaccination. These reactions probably result from hypersensitivity to some vaccine component; most reactions likely 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 immunoglobulin-E–mediated hypersensitivity 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 considered.

Although the 1976 swine influenza vaccine was associated with an increased incidence of GBS, evidence for a causal relationship with subsequent vaccines is less clear. During three or 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 increase in the relative risk and the increased number of cases in the second week after vaccination may have been the result of vaccination but also could have been the result of other factors. 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 Vaccination

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. Giving vaccine too far in advance should be avoided.

Children younger than nine years who have not been vaccinated previously should receive two doses of vaccine at least one month apart to maximize the likelihood of a satisfactory antibody response to all three vaccine antigens. The second dose should be administered before December, if possible. Vaccine should be offered to both children and adults up to and even after the time when influenza virus activity is documented in a community.

Antiviral Agents for Influenza A

Amantadine and rimantadine are effective only for type A influenza viruses. When administered prophylactically to healthy adults or children, both drugs are approximately 70 to 90 percent effective. Because antiviral agents taken prophylactically can prevent illness but not subclinical infection, some persons who take these drugs can still develop immune responses that will protect them when they are exposed to antigenically related viruses in later years.

In otherwise healthy adults, amantadine and rimantadine can reduce the severity and duration of signs and symptoms of influenza A illness when administered within 48 hours of illness onset. There is limited information on the use of amantadine and rimantadine in the treatment of children with influenza A virus. Amantadine is indicated for treatment and prophylaxis of adults and children one year of age and older. Rimantadine is approved for treatment and prophylaxis in adults but is approved only for prophylaxis in children.

Adverse reactions from amantadine and rimantadine rarely are severe; however, for some categories of patients, severe adverse reactions are more likely to occur. Amantadine has been associated with a higher incidence of adverse central nervous system reactions than rimantadine.

Use of Antiviral Agents as Prophylaxis

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 but vaccinated after influenza A activity has begun.

• Persons providing care to those at high risk.

• Persons with immunodeficiency.

• Persons for whom influenza vaccine is contraindicated.

• Other persons, including those who want to avoid 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 if given 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.

Amantadine- and rimantadine-resistant influenza A viruses can emerge when either of these drugs is used for treatment; amantadine-resistant strains are cross-resistant to rimantadine and vice versa. Data indicate that amantadine- and rimantadine-resistant viruses are no more virulent or transmissible than amantadine- and rimantadine-sensitive viruses. Resistant viruses have been isolated from persons who live at home or in an institution where other residents are taking or have recently taken amantadine or rimantadine as therapy. Persons who have influenza-like illness should avoid contact with uninfected persons as much as possible even if they are receiving treatment.

Persons who have influenza type A infection and who are treated with either drug can shed amantadine- or rimantadine-sensitive viruses early in the course of treatment, but can later shed drug-resistant viruses, especially after five to seven days of therapy. Such persons can benefit from therapy even when resistant viruses emerge; however, they also can transmit infection to other persons with whom they come in contact. Because of possible induction of amantadine or rimantadine resistance, 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 24 to 48 hours after symptoms disappear.

Selection of Drugs

Amantadine and rimantadine differ in their pharmacokinetic properties. Although both drugs can cause adverse reactions of the central nervous system and of the gastrointestinal system when administered to young, healthy adults at dosages of 200 mg per day, the incidence of central nervous system side effects is higher in persons taking amantadine than in those taking rimantadine. The incidence of gastrointestinal side effects is approximately 3 percent in persons taking either drug. Side effects associated with both drugs are usually mild and resolve after discontinuation of the drug. Side effects can diminish or disappear even after continued use of the drug. However, serious side effects have been observed (e.g., marked behavioral changes, delirium, hallucinations). These more severe side effects have been related to high plasma drug concentrations and have been observed most often in persons who have renal insufficiency, seizure disorders or certain psychiatric disorders and in elderly persons who have been taking amantadine as prophylaxis at a dosage of 200 mg per day. Lowering the dose reduces the side effects. Recommendations for reduced dosages for these groups of patients have been made.

Physicians should review the package insert before using amantadine or rimantadine for any patient. The patient's age, weight, renal function, use of other medications, presence of other medical conditions, indications for use of amantadine or rimantadine, and the potential for interaction with other medications must be considered.

The report in MMWR includes additional recommendations for the use of the influenza vaccine in persons with impaired renal function, in elderly persons, in persons who have liver disease, in persons who have seizure disorders, and in children.