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 2000–2001 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 ACIP recommendations cover the following areas: options for controlling influenza; the effectiveness of inactivated influenza vaccine; composition of the 2000–2001 influenza vaccine; vaccination of target groups; vaccination of specific populations; persons who should not be vaccinated; optimal timing for annual vaccination; administration of the influenza vaccine; side effects and adverse reactions of the vaccine; simultaneous administration of other vaccines; strategies for implementation of these recommendations in health care settings; evolving developments related to the influenza vaccine; use of antiviral agents for influenza; indications for the use of and considerations for the selection of amantadine, rimantadine, zanamivir and oseltamivir; and considerations for selection of these agents for treatment or prophylaxis. The recommendations also include sources of information on control of influenza.
The five principle changes in this year's recommendations include information on the following: the lowering of the age for universal vaccination from 65 to 50 years; the consideration of scheduling large, organized vaccination campaigns after mid-October because the availability of vaccine in any location cannot be assured consistently in the early fall; the 2000–2001 trivalent vaccine virus strains, which are A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Beijing/184/93-like strains; the addition of neuraminidase-inhibitor antiviral drugs; and a list of other influenza-related infection control documents for special populations.
The complete report of the ACIP recommendations is published in Morbidity and Mortality Weekly Report recommendations and reports series (MMWR Morb Mortal Wkly Rep 2000;49[RR-3]:1–28). The report is also available on 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 2000–2001 Influenza Vaccine
The trivalent vaccine for the 2000–2001 influenza season will include A/Moscow/10/99 (H3N2)-like, A/New Caledonia/20/99 (H1N1)-like, and B/Beijing/184/93-like antigens. For the A/Moscow/10/99 (H3N2)-like antigen, U.S. manufacturers will use the antigenically equivalent A/Panama/2007/99 (H3N2) virus and for the B/Beijing/184/93-like antigen, manufacturers will use the antigenically equivalent B/Yamanashi/166/98 virus; these viruses will be used because of their growth properties and because they are representative of currently circulating A (H3N2) and B viruses.
According to the ACIP committee, influenza vaccine is recommended for any person six months or older who, because of age or underlying medical condition, is at increased risk for complications of influenza. Health care workers and other persons who are in close contact with those in high-risk groups should receive the vaccine. Influenza vaccine may also be administered to any person at least six months of age to reduce the chance of influenza infection.
Target Groups for Vaccination
Vaccination is recommended for the following groups who are at increased risk for complications from influenza: persons 50 years and older; residents of nursing homes and other chronic-care facilities that house persons of any age with chronic medical conditions; adults and children with chronic disorders of the pulmonary or cardiovascular system, including asthma; adults and children who required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases, renal dysfunction, hemoglobinopathies or immunosuppression; children and teenagers who are receiving long-term aspirin therapy and therefore might be at risk for development of Reye's syndrome after influenza infection; and women who will be in the second or third trimester of pregnancy during the influenza season.
Other Groups to Consider for Vaccination
Pregnant women. Women who will be beyond the first trimester of pregnancy during the influenza season should receive the vaccination. Pregnant women who have medical conditions that increase their risk of complications from influenza should be vaccinated before the influenza season, regardless of the stage of pregnancy.
Because the currently available influenza vaccine is inactivated, many experts consider vaccination to be safe during any stage of pregnancy, although more data are needed to confirm this. Some experts prefer to administer influenza vaccine during the second trimester to avoid a coincidental association with spontaneous abortion, which commonly occurs during the first trimester, and because exposures to vaccines have traditionally been avoided during the first trimester.
Persons Infected with Human Immunodeficiency Virus (HIV). Limited information is available regarding the frequency and severity of influenza or the benefits of vaccination among persons with human immunodeficiency virus (HIV) infection. Some reports suggest that symptoms of influenza might be prolonged and the risk for complications from influenza increased for some persons with HIV infection. Influenza vaccination has produced substantial 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 with advanced HIV disease and low CD4 cell counts, vaccination might not induce protective antibody titers; a second dose of vaccine does not improve the immune response in these persons. Because influenza can cause serious illness and complications, and because vaccination can result in the production of protective antibody titers, vaccination will benefit many HIV-infected patients, including HIV-infected pregnant women.
Breast-feeding Mothers. Influenza vaccine does not affect the safety of mothers who are breast-feeding or their infants. Breast-feeding does not adversely affect the immune response and is not a contraindication for influenza vaccination.
Travelers. Persons who are at high risk for complications of influenza who were not vaccinated during the preceding fall or winter should consider receiving the influenza vaccine before travel if they plan to: (1) travel to the tropics, (2) travel with large organized tourist groups at any time of year or (3) travel to the Southern Hemisphere from April through September.
Persons at high risk who were vaccinated before travel during the previous season should be revaccinated with the current vaccine in the following fall or winter. Persons 50 years or older and others who are at high risk should visit their physicians before summer travel to discuss the symptoms and risks of influenza and the advisability of carrying antiviral medications for prophylaxis or treatment of influenza.
General Population. Influenza vaccine should be administered to any person who wants to reduce the likelihood of contracting influenza. The vaccine may be given to children as young as six months. Persons who provide essential community services should consider vaccination to minimize disruption of essential activities during outbreaks of influenza. Students and other persons who spend time in institutional settings should also be encouraged to receive the vaccine.
Persons Who Should Not Be Vaccinated
Influenza vaccine should not be given to persons who are known to have anaphylactic hypersensitivity to eggs or other components of the influenza vaccine without first consulting a physician. Use of an antiviral agent is an option for the prevention of influenza A among such persons. However, persons who have a history of anaphylactic hypersensitivity to the components of vaccine, but who are also at high risk for complications of influenza, can benefit from vaccination after appropriate allergy evaluation and desensitization.
Persons with acute febrile illness should not be vaccinated until their symptoms have abated. However, minor illnesses with or without fever do not contraindicate use of the influenza vaccine, particularly among children with mild upper respiratory tract infection or allergic rhinitis.
Timing of Annual Vaccination
Persons in high-risk groups should be vaccinated from the beginning of October through mid-November, because influenza activity in the United States generally peaks between late December and early March. While the vaccine usually becomes available in August or September, vaccine for the upcoming influenza season might not be available in some locations until later in the fall. In facilities such as nursing homes, administration of the vaccine should usually be avoided before October because antibody levels can begin to decline within a few months after vaccination.
Beginning each September, influenza vaccine should be offered to persons at high risk for influenza when they visit physicians for routine care or are hospitalized, as long as the vaccine is available. If regional influenza activity is expected to start before December, vaccination programs might begin as early as September. The influenza vaccine should be offered to unvaccinated persons even after influenza virus activity has been documented in a community and should continue to be offered throughout the influenza season.
Dosage recommendations for influenza vaccine vary according to age group. ACIP reports that among previously unvaccinated children nine years or younger, two doses administered at least one month apart are recommended for satisfactory antibody responses. If possible, the second dose should be given before December. Adults have little or no improvement in antibody response when a second dose is administered during the same season. Even when the current vaccine contains one or more of the antigens administered in previous years, annual vaccination with the current vaccine is necessary because immunity decreases in the year following vaccination.
Adults and older children should be vaccinated in the deltoid muscle with a needle one inch or more in length. Infants and children should be vaccinated in the anterolateral aspect of the thigh.
Side Effects and Adverse Reactions
When patients are told about potential side effects of vaccination, physicians should emphasize that inactivated influenza vaccine contains noninfectious killed viruses that cannot cause influenza and that coincidental respiratory disease unrelated to influenza vaccination can occur after vaccination. The most frequent side effect of vaccination is soreness at the vaccination site. The soreness affects 10 to 64 percent of patients and normally lasts up to two days. Local reactions are generally mild and rarely interfere with the person's ability to conduct daily activities.
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. Such reactions typically begin six to 12 hours after vaccination and persist for up to two days.
Allergic reactions such as hives, angioedema, allergic asthma and systemic anaphylaxis rarely occur after influenza vaccination, probably resulting from hypersensitivity to some component of the vaccine. Most reactions are caused by residual egg protein in the vaccine. Persons who develop hives, have swelling of the lips or tongue, or experience acute respiratory distress or collapse after eating eggs should be evaluated by a physician to determine if the vaccine should be used. Persons with documented immunoglobulin E-mediated hypersensitivity to eggs might also be at increased risk for allergic reaction to influenza vaccine. These persons should also consult a physician before vaccination.
While the 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barré syndrome (GBS), evidence of a causal relationship with subsequent vaccines is unclear. During three of four influenza seasons studied from 1977 through 1991, the overall relative risk estimates for GBS after vaccination were slightly elevated but were not statistically significant. Investigations to date suggest no large increase in GBS associated with influenza vaccines (other than the swine influenza vaccine in 1976) and that if influenza vaccine does pose a risk, it is probably small. The potential benefits of influenza vaccination in the prevention of serious illness, hospitalization and death greatly outweigh the possible risks for the development of vaccine-associated GBS. The average case fatality ratio of 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.
Potential New Vaccines
Intranasally administered, cold-adapted, live, attenuated, influenza virus vaccines are being developed in the United States. The viruses in these vaccines replicate in the upper respiratory tract and elicit a specific protective immune response. These viruses have been studied as monovalent, bivalent and trivalent formulations and consist of live viruses that induce minimal symptoms and replicate poorly at temperatures found in the lower respiratory tract. The possible advantages of these vaccines are their potential to induce a broad mucosal and systemic immune response, ease of administration and the acceptability of an intranasal route of administration compared with injectable vaccines.
Potential Addition of Children to Groups Recommended for Vaccination
In 1998, ACIP formed a working group to explore issues related to the potential expansion of recommendations for the use of influenza vaccine. The ACIP influenza working group is considering the impact of influenza in young children as well as the potential safety issues, and logistic and economic consequences of recommending routine vaccination of young healthy children.
Recommendations for the Use of Antiviral Agents for Influenza
While antiviral drugs for influenza are an important adjunct to influenza vaccine for the control and prevention of influenza, they should not be a substitute for vaccination. Four currently licensed antiviral agents are available in the United States: amantadine, rimantadine, zanamivir and oseltamivir.
Amantadine and rimantadine are chemically related antiviral drugs that are indicated for the prophylaxis and treatment of influenza A infection. However, they have no activity against influenza B viruses.
Zanamivir and oseltamivir are neuraminidase inhibitors that were approved in 1999 for the treatment of uncomplicated influenza A and B infections. Neither has been approved for prophylaxis. Zanamivir was approved for treatment of persons 12 years and older, and oseltamivir was approved for treatment of persons 18 years and older.
Antiviral Agents as Treatment
When administered to otherwise healthy adults within two days of the onset of illness, amantadine and rimantadine can reduce the duration of uncomplicated influenza A, and zanamivir and oseltamivir can reduce the duration of uncomplicated influenza A and B by approximately one day.
None of the four antiviral agents has been shown to be effective in preventing serious influenza-related complications, such as bacterial or viral pneumonia or exacerbation of chronic diseases. Evidence for the effectiveness of these four antiviral drugs is based mainly on studies of patients with uncomplicated influenza. Studies on the effectiveness of any of the four drugs for treatment in children are also limited.
To lower the emergence of antiviral drug-resistant viruses, treatment with amantadine or rimantadine for persons with 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 signs and symptoms have disappeared. The recommended duration of treatment with zanamivir or oseltamivir is five days.
Antiviral Agents as Prophylaxis
According to ACIP, chemoprophylaxis is not a substitute for vaccination. Amantadine and rimantadine are indicated for the prophylaxis of influenza A infection but are not effective against influenza B. When used as prophylaxis, these antiviral agents can prevent illness while permitting subclinical infection and the development of protective antibody against circulating influenza viruses. Zanamivir and oseltamivir have not been approved for prophylaxis, but recent community studies suggest that both drugs are similarly effective in preventing febrile, laboratory-confirmed influenza.
When determining the timing and duration for administration of amantadine or rimantadine for prophylaxis, factors of cost, compliance and potential side effects should be considered. Antiviral agents are recommended as prophylaxis for the following groups of persons:
Persons at high risk who are vaccinated after influenza activity has begun.
Persons who provide care to those at high risk.
Persons who have immunodeficiency, including those with HIV infection.
Other persons, such as those who wish to avoid influenza A illness.
Sources of Information on Influenza
Information on 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/weekly.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. State and local health departments should be consulted about the availability of influenza vaccine, access to vaccination programs, information about state or local influenza activity, and for reporting influenza outbreaks and receiving advice on control of outbreaks.