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Recommendations of the Immunization Practices Advisory Committee (ACIP) Prevention and Control of Influenza

These recommendations of the Immunization Practices Advisory Committee update for 1986-1987 the information on the vaccine and antiviral agent available for control of influenza (superseding MMWR 1985;34:261-8, 273-5). Changes include addition of statements about: (1) updating of the influenza strains in the vaccine for 1986-1987; (2) immunization and amantadine prophylaxis for household members who provide home care for high-risk persons; (3) optimal time for conducting routine vaccination programs; (4) concurrent administration of influenza vaccine and childhood vaccines; (5) immunization of children receiving long-term aspirin therapy; and (6) other sources of information about influenza and control measures.


Influenza A viruses are classified into subtypes based on two antigens: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, H3) and two subtypes of neuraminidase (N1, N2) are recognized among influenza A viruses that have caused wide-spread human disease. Immunity to these antigens, especially hemagglutinin, reduces the likelihood of infection and the severity of disease if infection does occur. However, there may be sufficient antigenic variation (antigenic drift) within the same subtype over time, so that infection or vaccination with one strain may not induce immunity to distantly related strains of the same subtype. Although influenza B viruses have shown much more antigenic stability than influenza A viruses, antigenic variation does occur. For these reasons, major epidemics of respiratory disease caused by new variants of influenza continue to occur, and the antigenic characteristics of current strains provide the basis for selecting virus strains included in each year's vaccine.

Typical influenza illness is characterized by abrupt onset of fever, sore throat, and nonproductive cough and, unlike many other common respiratory infections, can cause extreme malaise lasting several days. More severe disease can result from invasion of the lungs by influenza virus (primary viral pneumonia) or from secondary bacterial pneumonia. High attack rates of acute illness and the occurrence of lower respiratory tract complications usually result in dramatic increases in visits for outpatient care in physicians' offices, walk-in clinics, and emergency rooms by persons of all ages.

Individuals at high risk for influenza are poorly able to cope with the disease because of their ages or underlying health problems. Such high-risk persons are more likely to require hospitalization if infected. In one recent study, for example, hospitalization rates for adults with high-risk medical conditions increased during major epidemics by about twofold to fivefold in different age groups, reaching a maximum rate of about 800 excess hospital- izations per 100,000 high-risk persons. During influenza epidemics, normally healthy children and adults may also be hospitalized for influenza-related complications, but the relative increase in hospitalization rates is much less than for the high-risk groups.

A further indication of the impact of influenza epidemics is the signi- ficant increase in mortality that often occurs. Such excess mortality is not only a direct result of pneumonia, but also of cardiopulmonary or other chronic diseases that are exacerbated during influenza infection. Ten thousand or more excess deaths have been documented during each of 18 different epidemics from 1957 to 1985, with more than 40,000 excess deaths in each of several recent epidemics. Excess mortality was again documented during the 1985-1986 influenza season. Approximately 80%-90% of the excess deaths attributed to pneumonia and influenza during epidemics have occurred among persons 65 years of age or older, although influenza-associated deaths among children or previously healthy adults under 65 years of age are reported during major epidemics.

Because of the increasing proportion of elderly persons in the U.S. population, and because age and its associated chronic diseases are risk factors for severe influenza illness, the future toll from infuenza may increase unless control measures are used more vigorously than in the past. Younger populations at high risk for influenza-related complications are also increasing, due to such factors as the success of intensive-care units for neonates; better management of diseases, such as cystic fibrosis; and better survival rates for organ-transplant recipients.


The two presently available control measures for influenza are immunopro- phylaxis with vaccines and chemoprophylaxis or therapy with the antiviral drug, amantadine hydrochloride (Symmetrel(R)).

Vaccination of high-risk persons each year before the influenza season is the single most important influenza-control measure. Vaccination is likely to be highly cost-effective because (1) it is targeted at individuals for whom infection may have the most severe consequences and for whom there is often a higher-than-average potential for infection, and (2) it may be administered when such high-risk individuals routinely have contact with the health-care delivery system before the influenza season for causes other than acute respiratory infection, thereby permitting vaccine administration without special visits to physicians' offices or clinics. Recent reports indicate that achieving high vaccination rates in closed populations appears to induce herd immunity when there is a good match between vaccine and epidemic strains of virus. When outbreaks of influenza A do occur in closed populations, they may be stopped by amantadine prophylaxis of all residents. Other indications for prophylaxis (whether with vaccine or antiviral drug) include the strong desire of individuals to avoid influenza infection, reduce the severity of disease, or reduce their chances of transmitting influenza to high-risk persons with whom they have frequent contact in medical-care settings or at home.

Specific therapy for influenza A by treatment with amantadine is most likely to benefit individuals who promptly seek medical attention because of the abrupt onset of an acute respiratory infection with troublesome symptoms during an influenza A epidemic. For high-risk individuals for whom influenza vaccine has not been used or has not prevented infection, early treatment with amantadine should be effective in reducing the severity and duration of illness.

Influenza is known to cause nosocomial infections, and measures, such as isolating ill patients individually or in groups, limiting visitors, and avoiding elective admissions and surgery during an influenza outbreak, have been suggested to limit further virus transmission within institutions or hospitals. However, unlike amantadine use for outbreak control during influenza A epidemics, the effectiveness of these measures has not been demonstrated. Likewise, the effect on virus transmission of occasionally closing schools or classrooms during explosive outbreaks has not been established.


Influenza vaccines are made from highly purified egg-grown viruses that have been rendered noninfectious ("inactivated"). Most vaccines distributed in the United States have been chemically treated ("split virus" prepar- ations) to reduce the incidence of febrile reactions among children. Influenza vaccine contains three virus strains (two type A and one type B) representing influenza viruses presently circulating in the world and believed likely to occur in the United States next winter. The potency of present vaccines is such that (1) minimal systemic or febrile reactions are caused by the vaccine, but (2) nearly all vaccinated young adults develop hemagglutination-inhibition antibody titers likely to protect them against infection by strains like those in the vaccine and, often, by related variants that emerge. The elderly, the very young, and patients with certain chronic diseases may develop lower postvaccination antibody titers than young adults and thus be more susceptible to upper respiratory tract infection. Under these circumstances, however, influenza vaccine can still be effective in preventing lower respiratory tract involvement or other complications of influenza. Influenza vaccine will not prevent primary illnesses caused by other respiratory pathogens.


Influenza vaccine is recommended for high-risk persons 6 months of age or older (see below), for their medical-care personnel and primary providers of care in the home setting, for children receiving long-term aspirin therapy, and for other persons wishing to reduce their chances of acquiring influenza illness. Vaccine composition for 1986-1987 and doses are given in Table 1. Guidelines for the use of vaccine are given below for different segments of the population. Remaining 1985-1986 vaccine should not be used. Although the current influenza vaccine often contains one or more antigens used in previous years, immunity declines during the year following vaccination. Therefore, a history of vaccination in any previous year with a vaccine containing one or more antigens included in the current vaccine does not preclude the need for revaccination for the 1986-1987 influenza season to provide optimal protection.

During the past decade, data on influenza vaccine immunogenicity and side effects were generally obtained when vaccine was administered by the intra- muscular route. Because of a lack of adequate evaluation of recent influenza vaccines administered by other routes to high-risk persons, the preferred route of vaccination is intramuscular. The recommended site of vaccination is the deltoid muscle for adults and older children and the anterolateral aspect of the thigh for infants and young children.

High-Priority Target Groups for Special Vaccination Programs

  1. Groups at greatest medical risk of influenza-related complications.

Based on observations of morbidity and mortality, high-risk groups have been classified on the basis of priority, so available resources can be particu- larly directed toward organizing special programs to provide vaccine to those who may derive the greatest benefit. Active, targeted vaccination efforts are most necessary for the following two high-risk groups, with the objective of vaccinating at least 80% of each group.

  1. Adults and children with chronic disorders of the cardiovascular or pulmonary systems that are severe enough to have required regular medical follow-up or hospitalization during the preceding year.

  2. Residents of nursing homes and other chronic-care facilities (i.e., institutions housing patients of any age with chronic medical conditions).

    2. Groups at moderate medical risk of influenza-related complications.

After considering the needs of the above two target groups (1a and 1b), programs are desirable that make vaccine readily available to persons at moderately increased risk of serious illness compared with the general population. These include:

  1. Otherwise healthy individuals 65 years of age or older.

  2. Adults and children with chronic metabolic diseases (including diabetes mellitus), renal dysfunction, anemia, immunosuppression, or asthma that are severe enough to require regular medical follow-up or hospitalization during the preceding year.

  3. Children receiving long-term aspirin therapy, who may be at risk of developing Reye syndrome following influenza infection.

    3. Groups potentially capable of nosocomial transmission of influenza to

high-risk persons. During many winters, nosocomial outbreaks of influenza are reported. Although not proven, it is reasonable to believe that medical personnel who provide care to high-risk persons in health-care facilities, or family members, volunteer workers, or others who are the primary providers of care to a high-risk person in the home setting, can transmit influenza infec- tions to high-risk patients while they are themselves incubating infection, undergoing subclinical infection, or working despite the existence of mild symptoms. The potential for introducing influenza to high-risk persons should be reduced by vaccinating:

  1. Physicians, nurses, and other personnel who have extensive contact with high-risk patients (e.g., primary-care and certain specialty clinicians, staff of intensive-care units, particularly neonatal intensive-care units).

  2. Providers of care to high-risk persons in the home setting (e.g., family members, visiting nurses, volunteer workers).

Vaccination of Other Groups

  1. General population. Physicians should administer vaccine to any person

who wishes to reduce his/her chances of acquiring influenza infection. Persons who provide essential community services, such as employees of fire and police departments, are not considered at increased occupational risk of serious influenza illness but may be considered for vaccination programs designed to minimize the possible disruption of essential activities that can occur during severe epidemics.

2. Pregnant women. Pregnancy has not been demonstrated to be a risk factor for severe influenza infection, except in the largest pandemics of 1918-1919 and 1957-1958. However, a pregnant woman with a medical condition that increases her risk of complications from influenza should be vaccinated, as influenza vaccine is considered safe for pregnant women in the absence of a specific severe egg allergy. Nonetheless, when vaccine is given during pregnancy, waiting until after the first trimester is a reasonable precaution to minimize any concern over the theoretical possibility of teratogenicity. However, it may be undesirable to delay vaccination of a pregnant woman with a high-risk condition who will still be in the first trimester of pregnancy when influenza activity usually begins.

Persons Who Should Not Be Vaccinated

Inactivated influenza vaccine should not be given to persons who have an anaphylactic sensitivity to eggs (see below, Side Effects and Adverse Reactions ). Persons with acute febrile illnesses usually should not be vaccinated until their temporary symptoms have abated.

Timing of Influenza Vaccination Activities

The first sporadic laboratory-confirmed cases of influenza in the United States or U.S. territories are often documented in September or October; however, except in years of pandemic influenza (e.g., 1957 and 1968), high levels of influenza activity have not occurred in the contiguous United States before late December. Therefore, organized vaccination campaigns where high-risk persons are routinely accessible, such as in chronic-care facilities or worksites, may be optimally undertaken in November. Vaccination is desirable in September or October (1) if warranted by regional experience of earlier-than-normal epidemic activity (e.g., in Alaska); (2) for hospi- talized high-risk patients who should be vaccinated at the time of discharge (such patients should be vaccinated when discharged from September to the time influenza activity begins to decline in their community); or (3) for other persons recommended for vaccination who receive medical check-ups or treatment during the late or early fall and who may not be seen again until after November.

Children who have not been previously vaccinated require two doses of vaccine with at least 1 month between doses. Programs for childhood influenza vaccination should be scheduled so the second dose can be given before December. Vaccine can be given to both children and adults up to and even after influenza virus activity is documented in a region, although temporary chemophrophylaxis may be indicated when influenza outbreaks are occurring (see below, ANTIVIRAL AGENT FOR INFLUENZA A: AMANTADINE).

Strategies for Implementing Influenza Vaccine Recommendations

More effective programs for giving influenza vaccine to high-risk persons, well planned in advance, are needed in nursing homes and other chronic-care facilities, in physicans' offices, health-maintenance organi- zations, hospital settings, and employee-health clinics. Adults and children in high-priority target groups who do not reside in nursing homes or other chronic-care facilities should be scheduled to receive influenza vaccine at the time of their last regular medical follow-up before the influenza season (i.e., before December). High-risk persons not scheduled for regular medical appointments in the fall should be notified by their medical-care provider to come in specifically to receive influenza vaccine. Hospital discharge procedures each September-February should include influenza vaccination of high-risk patients. Medical-care personnel and auxiliary staff must be made aware of the importance of ensuring that no high-risk patient resides in or leaves a medical-care facility in the fall without being strongly urged to receive influenza vaccine and having the vaccine offered.

Educational materials (e.g., audio-visual tape) about influenza and its control are available for inservice training through state chapters of the American Lung Association (National Headquarters telephone {212} 315-8700). Black-and-white layouts that can be used to reproduce a brochure, "What You Should Know About Flu and Flu Shots," prepared by CDC, and copies of a report, "Implementation of Recommendations for Influenza Control," published in the MMWR (1985;34:639-43), are available on request by sending a pread- dressed mailing label to: Office of Public Inquiries, Building 1, Room B63, CDC, Atlanta, Georgia 30333.

Side Effects and Adverse Reactions

Because vaccines contain only noninfectious viruses, they cannot cause influenza. Occasional cases of respiratory disease following vaccination represent coincidental illnesses unrelated to influenza infection. The most frequent side effect of vaccination, which occurs in less than one-third of vaccinees, is soreness around the vaccination site for up to 1-2 days.

Systemic reactions have been of two types:

  1. Fever, malaise, myalgia, and other systemic symptoms of toxicity that, although infrequent, most often affect persons, such as young children, who have had no exposure to the influenza virus antigens contained in the vaccine. These reactions begin 6-12 hours after vaccination and can persist for 1-2 days.

  2. Immediate, presumably allergic, responses, such as flare and wheal or various respiratory tract symptoms of hypersensitivity, that may occur extremely rarely after influenza vaccination. These symptoms probably result from sensitivity to some vaccine component--most likely residual egg protein. Although current influenza vaccines contain only a small quantity of egg protein, the vaccine is presumed capable of inducing hypersensitivity reactions in individuals with anaphylactic hypersensitivity to eggs, and such persons should not be given influenza vaccine. This includes individuals who, after eating eggs, develop swelling of the lips or tongue or experience acute respiratory distress or collapse or persons who have a documented IgE-mediated hypersensitivity reaction to eggs, including those who, from occupa- tional exposure to egg protein, have developed evidence of occupa- tional asthma or other allergic response. Unlike the 1976 swine influenza vaccine, subsequent vaccines, which have been prepared from other virus strains, have not been associated with an increased frequency of Guillain-Barre syndrome. Although it has been reported that influenza vaccination may inhibit the clearance of warfarin and theophylline, further studies have consistently failed to show any adverse effects of influenza vaccination in patients taking these drugs.

Simultaneous Administration of Other or Childhood Vaccines

There is considerable overlap in the target groups for influenza and pneumococcal vaccination. Pneumococcal and influenza vaccines can be given at the same time at different sites without increased side effects, but it should be emphasized that, whereas influenza vaccine is given annually, pneumococcal vaccine should be given only once. Detailed immunization records, which should be provided to each patient, will help ensure that additional doses of pneumococcal vaccine are not given.

Because children are accessible at times when pediatric vaccines are administered, it may be desirable to simultaneously administer influenza vaccine, if indicated, with routine pediatric vaccine but at different sites. Although studies have not been done, no diminution of immunogenicity or enhancement of adverse reactions should be expected.


The only drug currently approved in the United States for the specific prophylaxis and therapy of influenza virus infections is amantadine hydro- chloride (Symmetrel(R)). This drug appears to interfere with the uncoating step in the virus replication cycle and also reduces virus shedding. Amantadine is 70%-90% effective in preventing illnesses caused by circulating strains of type A influenza viruses, but it is not effective against type B influenza. When administered within 24-48 hours after onset of illness, amantadine has been shown to reduce the duration of fever and other systemic symptoms with a more rapid return to routine daily activities and improvement in peripheral airway function. Since it may not prevent actual infection, persons who take the drug may still develop immune responses that will protect them when exposed to antigenically related viruses.

Considerable evidence shows that amantadine chemoprophylaxis is effective against influenza A; however, under most circumstances, it should not be used in lieu of vaccination because (1) it confers no protection against influenza B and (2) patient compliance could be a problem for continuous administration throughout epidemic periods, which generally last 6-12 weeks. Optimal use of amantadine will be improved by increasing the availability of rapid viral diagnostic tests and improving the dissemination of information about where influenza A virus infections have been confirmed by laboratory diagnosis. Such information is now available to public health officials by computer telecommunication from CDC, in addition to being reported throughout the influenza season in the MMWR.

Amantadine Prophylaxis Recommendations

Amantadine prophylaxis is particularly recommended to control presumed influenza A outbreaks. The drug should be given as early as possible after recognition of an outbreak in an effort to reduce the spread of the infection. Contingency planning for influenza outbreaks in institutions is needed to establish specific steps for rapid administration of amantadine to residents of chronic-care facilities, when appropriate, including obtaining physicians' orders on short notice. When the decision is made to give amantadine for outbreak control, it is desirable to administer the drug to all residents of the affected institution, taking into account dosage recom- mendations and precautions given below and in the drug's package insert. It is also recommended that amantadine prophylaxis be offered to unvaccinated staff who provide care to high-risk residents of chronic-care institutions or hospitals experiencing a presumed influenza A outbreak to reduce spread of virus and to minimize disruption of patient care.

Amantadine prophylaxis is also recommended in the following situations:

  1. As an adjunct to late immunization of high-risk individuals. It is not too late to immunize even when influenza A is known to be in the community. However, since the development of an antibody response following vaccination takes about 2 weeks, amantadine should be used in the interim. The drug does not interfere with antibody response to the vaccine.

  2. To reduce spread of virus and maintain care for high-risk persons in the home setting. Persons who play a major role in providing care for high-risk persons in the home setting (e.g., family members, visiting nurses, volunteer workers) should also receive amantadine for prophy- laxis when influenza A virus outbreaks occur in their communities, if such persons have not been appropriately immunized.

  3. For immunodeficient persons. To supplement protection afforded by vaccination, chemoprophylaxis is also indicated for high-risk patients who may be expected to have a poor antibody response to influenza vaccine, e.g., those with severe immunodeficiency.

  4. For persons for whom influenza vaccine is contraindicated. Chemopro- phylaxis throughout the influenza season is appropriate for those few high-risk individuals for whom influenza vaccine is contraindicated because of anaphylactic hypersensitivity to egg protein or prior severe reactions associated with influenza vaccination. Amantadine can also be used prophylactically in other situations (e.g.,

unimmunized members of the general population who wish to avoid influenza A illness). This decision should be made on an individual basis.


Amantadine should be considered for therapeutic use, particularly for persons in the high-risk groups who develop an illness compatible with influenza during known or suspected influenza A activity in the community. The drug should be given within 24-48 hours of onset of illness and should be continued until 48 hours after resolution of signs and symptoms.

Precautions for the Use of Amantadine

Special precautions should be taken when amantadine is administered to persons with impaired renal function or those with an active seizure disorder (see below). The safety and efficacy of amantadine for children under 1 year of age have not been fully established.


The usual adult dosage of amantadine is 200 mg/day; splitting the dose into 100 mg twice daily may reduce the incidence of side effects (Table 2). Amantadine is not metabolized and is excreted unchanged in the urine. Because renal function normally declines with age, and because side effects have been reported more frequently among older persons, a reduced dosage of 100 mg/day is generally advisable for persons aged 65 years or older to minimize the risk of toxicity. Persons 10-64 years old with an active seizure disorder may also be at risk of increased frequency of seizures when given amantadine at 200 mg/day rather than 100 mg/day.

Side Effects and Adverse Reactions

Five percent to 10% of otherwise healthy adults taking amantadine report side effects such as insomnia, lightheadedness, irritability, and difficulty concentrating. These and other side effects (see package insert) may be more pronounced among patients with underlying diseases, particularly those common among the elderly; provisions for careful monitoring are needed for these individuals so that adverse effects may be recognized promptly, and the drug reduced in dosage or discontinued, if needed. Since amantadine is not metabolized, toxic levels can occur when renal function is sufficiently impaired.


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