Prevention and Control of Influenza

Recommendations of the Advisory Committee on Immunization Practices (ACIP)

Biology of Influenza

Influenza A and B are the two types of influenza viruses that cause epidemic human disease (25). Influenza A viruses are further categorized into subtypes on the basis of two surface antigens: hemagglutinin and neuraminidase. Influenza B viruses are not categorized into subtypes. Since 1977, influenza A (H1N1) viruses, influenza A (H3N2) viruses, and influenza B viruses have circulated globally. In 2001, influenza A (H1N2) viruses that probably emerged after genetic reassortment between human A (H1N1) and A (H3N2) viruses began circulating widely. Both influenza A and B viruses are further separated into groups on the basis of antigenic characteristics. New influenza virus variants result from frequent antigenic change (i.e., antigenic drift) resulting from point mutations that occur during viral replication. Influenza B viruses undergo antigenic drift less rapidly than influenza A viruses.

Immunity to the surface antigens, particularly the hemagglutinin, reduces the likelihood of infection and severity of disease if infection occurs (26). Antibody against one influenza virus type or subtype confers limited or no protection against another type or subtype of influenza. Furthermore, antibody to one antigenic variant of influenza virus might not completely protect against a new antigenic variant of the same type or subtype (27). Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual incorporation of one or more new strains in each year's influenza vaccine. More dramatic antigenic changes, or shifts, occur less frequently and can result in the emergence of a novel influenza virus with the potential to cause a pandemic.

Clinical Signs and Symptoms of Influenza

Influenza viruses are spread from person to person, primarily through respiratory droplet transmission (e.g., when an infected person coughs or sneezes in close proximity to an uninfected person) (25). The typical incubation period for influenza is 1--4 days, with an average of 2 days (28). Adults can be infectious from the day before symptoms begin through approximately 5 days after illness onset. Children can be infectious for >10 days after the onset of symptoms, and young children also can shed virus before their illness onset. Severely immunocompromised persons can shed virus for weeks or months (29--32).

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) (33). Among children, otitis media, nausea, and vomiting also are commonly reported with influenza illness (34--36). Uncomplicated influenza illness typically resolves after 3--7 days for the majority of persons, although cough and malaise can persist for >2 weeks. However, among certain persons, influenza can exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease), lead to secondary bacterial pneumonia or primary influenza viral pneumonia, or occur as part of a coinfection with other viral or bacterial pathogens (37). Young children with influenza virus infection can have initial symptoms mimicking bacterial sepsis with high fevers (37,38), and febrile seizures have been reported in up to 20% of children hospitalized with influenza virus infection (35,39). Influenza virus infection also has been uncommonly associated with encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome (35,37,40,41).

Respiratory illnesses caused by influenza viruses are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone (see Role of Laboratory Diagnosis). Reported sensitivities and specificities of clinical definitions of influenza infection that include fever and cough in studies primarily among adults have ranged from 63% to 78% and 55% to 71%, respectively, compared with viral culture (42,43). Sensitivity and predictive value of clinical definitions can vary, depending on the degree of co-circulation of other respiratory pathogens and the level of influenza activity (44). A study of older nonhospitalized patients determined that the presence of fever, cough, and acute onset had a positive predictive value of only 30% for influenza (45), whereas a study of hospitalized older patients with chronic cardiopulmonary disease determined that a combination of fever, cough, and illness of <7 days was 78% sensitive and 73% specific for influenza (46). A study of vaccinated older persons with chronic lung disease indicated that cough was not predictive of influenza virus infection, although having a fever or feverishness was 68% sensitive and 54% specific for influenza virus infection (47). These results highlight the challenges of identifying influenza illness in the absence of laboratory confirmation.

Hospitalizations and Deaths from Influenza

The risks for complications, hospitalizations, and deaths from influenza are higher among persons aged >65 years, young children, and persons of any age with certain underlying health conditions (see Persons at Increased Risk for Complications) than among healthy older children and younger adults (1,6,8,48--56). Estimated rates of influenza-associated hospitalizations have varied substantially by age group in studies conducted during different influenza epidemics (Table 1).

Among children aged <5 years, hospitalization rates have ranged from approximately 500/100,000 children for those with high-risk medical conditions to 100/100,000 children for those without high-risk medical conditions (57--60). Hospitalization rates among children aged <24 months are comparable to rates reported among persons aged >65 years (59,60) (Table 1).

During seasonal influenza epidemics from 1979--80 through 2000--01, the estimated overall number of influenza-associated hospitalizations in the United States ranged from approximately 54,000 to 430,000/epidemic. An average of approximately 226,000 influenza-related excess hospitalizations occurred per year, and 63% of all hospitalizations occurred among persons aged >65 years (61). Since the 1968 influenza A (H3N2) virus pandemic, the number of influenza-associated hospitalizations is generally greater during seasonal influenza epidemics caused by type A (H3N2) viruses than seasons in which other influenza virus types predominate (62).

Influenza-related deaths can result from pneumonia and from exacerbations of cardiopulmonary conditions and other chronic diseases. Deaths of adults aged >65 years account for >90% of deaths attributed to pneumonia and influenza (1,54). In one study, approximately 19,000 influenza-associated pulmonary and circulatory deaths per influenza season occurred during 1976--1990, compared with approximately 36,000 deaths during 1990--1999 (1). Estimated rates of influenza-associated pulmonary and circulatory deaths/100,000 persons were 0.4--0.6 among persons aged 0--49 years, 7.5 among persons aged 50--64 years, and 98.3 among persons aged >65 years. In the United States, the number of influenza-associated deaths has increased in part because the number of older persons is increasing, particularly persons aged >85 years (63). In addition, influenza seasons in which influenza A (H3N2) viruses predominate are associated with higher mortality (64); influenza A (H3N2) viruses predominated in 90% of influenza seasons during 1990--1999, compared with 57% of influenza seasons during 1976--1990 (1).

Deaths from influenza are uncommon among children both with and without high-risk conditions, but do occur (65,66). A study that modeled influenza-related deaths estimated that an average of 92 deaths (0.4 deaths per 100,000) occurred among children aged <5 years annually during the 1990s, compared with 32,651 deaths (98.3 per 100,000) among adults aged >65 years (1). Of 153 laboratory-confirmed influenza-related pediatric deaths reported from 40 states during the 2003--04 influenza season, 96 (63%) were among children aged <5 years. Sixty-four (70%) of the 92 children aged 2--17 years with influenza who died had no underlying medical condition previously associated with an increased risk for influenza-related complications (67).

Options for Controlling Influenza

In the United States, the primary option for reducing the effect of influenza is through annual vaccination. Inactivated (i.e., killed virus) influenza vaccines and LAIV are licensed and available for use in the United States (see Recommendations for Using Inactivated and Live, Attenuated Influenza Vaccines). Vaccination coverage can be increased by administering vaccine to persons during hospitalizations or routine health-care visits, as well as at pharmacies, grocery stores, workplaces, or other locations in the community before the influenza season, therefore making special visits to physicians' offices or clinics unnecessary. Achieving increased vaccination rates among persons living in closed settings (e.g., nursing homes and other chronic-care facilities) and among staff can reduce the risk for outbreaks (13), especially when vaccine and circulating strains are well-matched. Vaccination of health-care workers and other persons in close contact with persons at increased risk for severe influenza illness also can reduce transmission of influenza and subsequent influenza-related complications. Antiviral drugs used for chemoprophylaxis or treatment of influenza are adjuncts to vaccine (see Recommendations for Using Antiviral Agents for Influenza) but are not substitutes for annual vaccination.

Influenza Vaccine Composition

Both the inactivated and live, attenuated vaccines prepared for the 2006--07 season will include A/New Caledonia/20/1999 (H1N1)-like, A/Wisconsin/67/2005 (H3N2)-like, and B/Malaysia/2506/2004-like antigens (for the A/Wisconsin/67/2005 [H3N2]-like antigen, manufacturers may use the antigenically equivalent A/Hiroshima/52/2005 virus, and for the B/ Malaysia/2506/2004-like antigen, manufacturers may use the antigenically equivalent B/Ohio/1/2005 virus). These viruses will be used because they are representative of influenza viruses that are anticipated to circulate in the United States during the 2006--07 influenza season and have favorable growth properties in eggs. Because circulating influenza A (H1N2) viruses are reassortants of influenza A (H1N1) and A (H3N2) viruses, antibodies directed against influenza A (H1N1) and influenza (H3N2) vaccine strains should provide protection against the circulating influenza A (H1N2) viruses. Influenza viruses for both TIV and LAIV are initially grown in embryonated hens eggs, and, therefore, might contain limited amounts of residual egg protein. Therefore, persons with a history of severe hypersensitivity, such as anaphylaxis, to eggs should not receive influenza vaccine.

For the inactivated vaccines, the vaccine viruses are made noninfectious (i.e., inactivated or killed) (68). Only subvirion and purified surface antigen preparations of the inactivated vaccine are available. Manufacturing processes vary by manufacturer. Manufacturers might use different compounds to inactivate influenza viruses and add antibiotics to prevent bacterial contamination. Package inserts should be consulted for additional information.

Comparison of LAIV with Inactivated Influenza Vaccine

Both inactivated influenza vaccine and LAIV are available. Although both types of vaccines are effective, the vaccines differ in several aspects (Table 2).

Major Similarities

Both LAIV and inactivated influenza vaccines contain strains of influenza viruses that are antigenically equivalent to the annually recommended strains: one influenza A (H3N2) virus, one A (H1N1) virus, and one B virus. Each year, one or more virus strains might be changed on the basis of global surveillance for influenza viruses and the emergence and spread of new strains. Viruses for both vaccines are grown in eggs. Both vaccines are administered annually to provide optimal protection against influenza virus infection (Table 2).

Major Differences

Inactivated influenza vaccine contains killed viruses, and thus cannot produce signs or symptoms of influenza virus infection. In contrast, LAIV contains live, attenuated viruses and, therefore, has a potential to produce mild signs or symptoms related to influenza virus infection. LAIV is administered intranasally by sprayer, whereas inactivated influenza vaccine is administered intramuscularly by injection. LAIV is more expensive than inactivated influenza vaccine, although the price differential between inactivated vaccine and LAIV has decreased for the 2006--07 season. LAIV is approved only for use among healthy persons aged 5--49 years; inactivated influenza vaccine is approved for use among persons aged >6 months, including those who are healthy and those with chronic medical conditions (Table 2).

Efficacy and Effectiveness of Inactivated Influenza Vaccine

The effectiveness of inactivated influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient, the degree of similarity between the viruses in the vaccine and those in circulation, and the outcome being measured. Vaccine efficacy and effectiveness studies might have various endpoints, including the prevention of medically attended acute respiratory illness (MAARI), prevention of culture-positive influenza virus illness, prevention of influenza or pneumonia-associated hospitalizations or deaths, seroconversion to vaccine serotypes, or prevention of seroconversion to circulating influenza virus subtypes. High postvaccination hemagglutination inhibition antibody titers develop in the majority of vaccinated children and young adults (69--71). These antibodies are protective against illness caused by strains that are antigenically similar to those strains of the same type or subtype included in the vaccine (70--73).

Children. Children aged >6 months usually acquire protective levels of anti-influenza antibody against specific influenza virus strains after influenza vaccination (69,70,74--79), although the antibody response among children at high risk for influenza-related complications might be lower than among healthy children (80,81). A 2-year randomized study of children aged 6--24 months determined that 89% of children seroconverted to all three vaccine strains during both years (82). During year 1, among 411 children, vaccine efficacy was 66% (95% confidence interval [CI] = 34%--82%) against culture-confirmed influenza (attack rates: 5.5% and 15.9% among vaccine and placebo groups, respectively). During year 2, among 375 children, vaccine efficacy was -7% (CI = -247%--67%; attack rates: 3.6% and 3.3% among vaccine and placebo groups, respectively); the second year exhibited lower attack rates overall and was considered a mild season. In both years of this study, the vaccine strains were well- matched to the circulating influenza virus strains.

A randomized study among children aged 1--15 years also demonstrated that inactivated influenza vaccine was 77% and 91% effective against influenza respiratory illness during H3N2 and H1N1 years, respectively (71). One study documented a vaccine efficacy of 56% against influenza illness among healthy children aged 3--9 years (83), and another study determined vaccine efficacy against influenza type B infection and influenza type A infection of 22%--54% and 60%--78% among children with asthma aged 2--6 years and 7--14 years, respectively (84). Two studies have documented that TIV vaccine decreases the incidence of influenza-associated otitis media among young children by approximately 30% (16,17), whereas a third study determined that vaccination did not reduce the burden of acute otitis media (82).

Effectiveness of One Dose versus Two Doses of Influenza Vaccine Among Previously Unvaccinated Children Aged <9 Years. Vaccine effectiveness is lower among previously unvaccinated children aged <9 years if they have only received 1 dose of influenza vaccine, compared with children who have received 2 doses. A retrospective study among approximately 5,000 children aged 6--23 months conducted during a year with a suboptimal vaccine match indicated vaccine effectiveness of 49% against medically attended, clinically diagnosed pneumonia or influenza among children who had received 2 doses of influenza vaccine. No effectiveness was demonstrated among children who had received only 1 dose of influenza vaccine, illustrating the importance of administering 2 doses of vaccine to previously unvaccinated children aged <9 years (85). Similar results were observed in a case-control study of children aged 6--59 months with laboratory-confirmed influenza (86). A study assessing protective antibody responses after 1 and 2 doses of vaccine among vaccine-naive children aged 5--8 years also demonstrated the importance of compliance with the 2-dose recommendation (87). When the vaccine antigens do not change from one season to the next, priming with a single dose of vaccine in the spring, followed by a dose in the fall might result in similar antibody responses to a 2-dose regimen in the fall (88,89).

Adults Aged <65 Years. When the vaccine and circulating viruses are antigenically similar, influenza vaccine typically prevents influenza illness among approximately 70%--90% of healthy adults aged <65 years (9,12,90,91). Vaccination of healthy adults also has resulted in decreased work absenteeism and decreased use of health-care resources, including use of antibiotics, when the vaccine and circulating viruses are well-matched (9--12,91,92). In a case-control study of adults aged 50--64 years with laboratory-confirmed influenza during the 2003--04 season when the vaccine and circulating viruses were not well-matched, vaccine effectiveness was estimated to be 52% among healthy persons and 38% among those with one or more high-risk conditions (93).

Adults Aged >65 Years. An important benefit of the influenza vaccine is its ability to help prevent secondary complications and reduce the risk for influenza-related hospitalization and death among adults aged >65 years with and without high-risk medical conditions (e.g., heart disease and diabetes) (13--15,18,94,95). Older persons and persons with certain chronic diseases might have lower postvaccination antibody titers than healthy young adults and can remain susceptible to influenza virus infection and influenza-related upper respiratory tract illness (96--98). A randomized trial among noninstitutionalized persons aged >60 years reported a vaccine efficacy of 58% against influenza respiratory illness but indicated that efficacy might be lower among those aged >70 years (99). However, among older persons not living in nursing homes or similar chronic-care facilities, influenza vaccine is 30%--70% effective in preventing hospitalization for pneumonia and influenza (15,100). Among older persons who reside in nursing homes, influenza vaccine is most effective in preventing severe illness, secondary complications, and deaths. In this population, the vaccine can be 50%--60% effective in preventing influenza-related hospitalization or pneumonia and 80% effective in preventing influenza-related death, although the effectiveness in preventing influenza illness often ranges from 30% to 40% (101--103).

Efficacy and Effectiveness of LAIV

The immunogenicity of the approved LAIV has been assessed in multiple studies (104--110), which included approximately 100 children aged 5--17 years and approximately 300 adults aged 18--49 years. LAIV virus strains replicate primarily in nasopharyngeal epithelial cells. The protective mechanisms induced by vaccination with LAIV are not completely understood but appear to involve both serum and nasal secretory antibodies. No single laboratory measurement closely correlates with protective immunity induced by LAIV.

Healthy Children. A randomized, double-blind, placebo-controlled trial among 1,602 healthy children initially aged 15--71 months assessed the efficacy of trivalent LAIV against culture-confirmed influenza during two seasons (111,112). This trial included subsets of 238 healthy children (163 vaccinees and 75 placebo recipients) aged 60--71 months who received 2 doses and 74 children (54 vaccinees and 20 placebo recipients) aged 60--71 months who received a single dose during season one, and a subset of 544 children (375 vaccinees and 169 placebo recipients) aged 60--84 months during season two. Children who continued in the study remained in the same study group. In season one, when vaccine and circulating virus strains were well-matched, efficacy was 93% for participants who received 2 doses of LAIV. In season two, when the A (H3N2) component was not well-matched between vaccine and circulating virus strains, efficacy was 86% overall. The vaccine was 92% efficacious in preventing culture-confirmed influenza during the two-season study. Other results included a 27% reduction in febrile otitis media and a 28% reduction in otitis media with concomitant antibiotic use. Receipt of LAIV also resulted in 21% fewer febrile illnesses. A review of LAIV effectiveness in children aged 18 months--18 years found effectiveness against MAARI of 18% but greater estimated efficacy levels: 92% against influenza A (H1N1) and 66% against an influenza B drift variant (113).

Healthy Adults. A randomized, double-blind, placebo-controlled trial among 4,561 healthy working adults aged 18--64 years assessed multiple endpoints, including reductions in self-reported respiratory tract illness without laboratory confirmation, absenteeism, health-care visits, and medication use during peak and total influenza outbreak periods (114). The study was conducted during the 1997--98 influenza season, when the vaccine and circulating A (H3N2) strains were not well-matched. During peak outbreak periods, no difference in febrile illnesses between LAIV and placebo recipients was observed. However, vaccination was associated with reductions in severe febrile illnesses of 19% and febrile upper respiratory tract illnesses of 24%. Vaccination also was associated with fewer days of illness, fewer days of work lost, fewer days with health-care--provider visits, and reduced use of prescription antibiotics and over-the-counter medications. Among a subset of 3,637 healthy adults aged 18--49 years, LAIV recipients (n = 2,411) had 26% fewer febrile upper-respiratory illness episodes; 27% fewer lost work days as a result of febrile upper respiratory illness; and 18%--37% fewer days of health-care--provider visits caused by febrile illness, compared with placebo recipients (n = 1,226). Days of antibiotic use were reduced by 41%--45% in this age subset.

A randomized, double-blind, placebo-controlled challenge study among 92 healthy adults (LAIV, n = 29; placebo, n = 31; inactivated influenza vaccine, n = 32) aged 18--41 years assessed the efficacy of both LAIV and inactivated vaccine (115). The overall efficacy of LAIV and inactivated influenza vaccine in preventing laboratory-documented influenza from all three influenza strains combined was 85% and 71%, respectively, on the basis of experimental challenge by viruses to which study participants were susceptible before vaccination. The difference in efficacy between the two vaccines was not statistically significant.

Cost-Effectiveness of Influenza Vaccine

Influenza vaccination can reduce both health-care costs and productivity losses associated with influenza illness. Studies of influenza vaccination of persons aged >65 years conducted in the United States have reported substantial reductions in hospitalizations and deaths and overall societal costs savings (15,100,104). Studies of adults aged <65 years have indicated that vaccination can reduce both direct medical costs and indirect costs from work absenteeism (8,10--12,91,116). Reductions of 13%--44% in health-care--provider visits, 18%--45% in lost workdays, 18%--28% in days working with reduced effectiveness, and 25% in antibiotic use for influenza-associated illnesses have been reported (10,12,117,118). One cost-effectiveness analysis estimated a cost of approximately $60--$4,000/illness averted among healthy persons aged 18--64 years, depending on the cost of vaccination, the influenza attack rate, and vaccine effectiveness against influenza-like illness (ILI) (91). Another cost-benefit economic study estimated an average annual savings of $13.66/person vaccinated (119). In the second study, 78% of all costs prevented were costs from lost work productivity, whereas the first study did not include productivity losses from influenza illness.

Economic studies specifically evaluating the cost-effectiveness of vaccinating persons aged 50--64 years are not available, and the number of studies that examine the economics of routinely vaccinating children with TIV or LAIV are limited (8,120--123). However, in a study of inactivated vaccine that included all age groups, cost utility (i.e., cost per year of healthy life gained) improved with increasing age and among those with chronic medical conditions (8). Among persons aged >65 years, vaccination resulted in a net savings per quality-adjusted life year (QALY) gained, whereas among younger age groups, vaccination resulted in costs of $23--$256/QALY.

In addition to estimating the economic cost associated with influenza disease, studies have assessed the public's perception of preventing influenza morbidity. Less than half of respondents to a survey on public perception of the value of preventing influenza morbidity reported that they would trade any time from their own life to prevent a case of uncomplicated influenza in a hypothetical child (124). When asked about their willingness to pay to prevent a hypothetical child from having an uncomplicated case of influenza, the median willingness-to-pay amount was $100 for a child aged 14 years and $175 for a child aged 1 year (124).

Vaccination Coverage Levels

One of the national health objectives for 2010 is to achieve an influenza vaccination coverage level of 90% for persons aged >65 years (objective no. 14-29a) (125). Among persons aged >65 years, influenza vaccination levels increased from 33% in 1989 (126) to 66% in 1999 (127), surpassing the Healthy People 2000 objective of 60% (128). Vaccination coverage in this group reached the highest levels recorded (68%) during the 1999--00 influenza season. This estimate was made using the percentage of adults reporting influenza vaccination during the previous 12 months in the National Health Interview Survey (NHIS). The NHIS administered during the first and second quarters of each calendar year was used as a proxy measure of influenza vaccination coverage for the previous influenza season (127). Possible reasons for increases in influenza vaccination levels among persons aged >65 years include 1) greater acceptance of preventive medical services by practitioners; 2) increased delivery and administration of vaccine by health-care providers and sources other than physicians; 3) new information regarding influenza vaccine effectiveness, cost-effectiveness, and safety; and 4) initiation of Medicare reimbursement for influenza vaccination in 1993 (8,14,15,101,102,129,130). Since 1997, influenza vaccination levels have increased more slowly, with an average annual percentage increase of 4% from 1988--89 to 1996--97 versus 1% from 1996--97 to 1998--99. In 2000, a substantial delay in influenza vaccine availability and distribution, followed by a less severe delay in 2001 likely contributed to the lack of progress. However, the slowing of the increase in vaccination levels began before 2000 and is not fully understood.

Estimated national influenza vaccine coverage in 2004 among persons aged >65 years and 50--64 years was 65% and 36%, respectively, based on 2004 NHIS data (Table 3). The estimated vaccination coverage among adults with high-risk conditions aged 18--49 years and 50--64 years was 26% and 46%, respectively, substantially lower than the Healthy People 2000 and 2010 objective of 60% (125,128). Continued annual monitoring is needed to determine the effects of vaccine supply delays and shortages, changes in influenza vaccination recommendations and target groups for vaccination, reimbursement rates for vaccine and vaccine administration, and other factors related to vaccination coverage among adults and children. New strategies to improve coverage will be needed to achieve the Healthy People 2010 objective (21,22).

Reducing racial and ethnic health disparities, including disparities in vaccination coverage, is an overarching national goal (125). Although estimated influenza vaccination coverage for the 1999--00 season reached the highest levels recorded among older black, Hispanic, and white populations, vaccination levels among blacks and Hispanics continue to lag behind those among whites (127,131). Estimated vaccination coverage levels based on 2004 NHIS data among persons aged >65 years were 67% among non-Hispanic whites, 45% among non-Hispanic blacks, and 55% among Hispanics (CDC, unpublished data, 2006). Among Medicare beneficiaries, unequal access to care might not be the only factor in contributing toward disparity levels in influenza vaccination; other key factors include having patients that actively seek vaccination and providers that recommend vaccination (132,133).

In 1997 and 1998, vaccination coverage estimates among nursing home residents were 64%--82% and 83%, respectively (134,135). The Healthy People 2010 goal is to achieve influenza vaccination of 90% among nursing home residents, an increase from the Healthy People 2000 goal of 80% (125,128).

Reported vaccination levels are low among children at increased risk for influenza complications. One study conducted among patients in health maintenance organizations (HMOs) documented influenza vaccination percentages ranging from 9% to 10% among children with asthma (136). A 25% vaccination level was reported among children with severe to moderate asthma who attended an allergy and immunology clinic (137). However, a study conducted in a pediatric clinic demonstrated an increase in the vaccination percentage of children with asthma or reactive airways disease from 5% to 32% after implementing a reminder/recall system (138). One study documented 79% vaccination coverage among children attending a cystic fibrosis treatment center (139). According to 2004 National Immunization Survey data, during the second year of the encouragement for vaccination of children aged 6--23 months, 18% received one or more influenza vaccinations and 8.4% received 2 doses if they were previously unvaccinated (140). A rapid analysis of influenza vaccination coverage levels among members of an HMO in Northern California determined that in 2004--05, the first year of the recommendation for vaccination of children aged 6--23 months, their coverage level reached 57% (141). Data from the Behavioral Risk Factor Surveillance System (BRFSS) collected in February 2005 indicated a national estimate of 48% vaccination coverage for 1 or more doses among children aged 6--23 months and 35% coverage among children aged 2--17 years who had one or more high-risk medical conditions during the 2004--05 season (142). Increasing vaccination coverage among persons who have high-risk conditions and are aged <65 years, including children at high risk, is the highest priority for expanding influenza vaccine use. As has been observed for older adults, a physician recommendation for vaccination and the perception that getting a child vaccinated "is a smart idea" were positively associated with likelihood of vaccination of children aged 6--23 months (143).

Annual vaccination is recommended for health-care workers. Nonetheless, NHIS 2004 survey data indicated a vaccination coverage level of only 42% among health-care workers (CDC, unpublished data, 2006). Vaccination of health-care workers has been associated with reduced work absenteeism (9) and fewer deaths among nursing home patients (144,145) and is a high priority for reducing the effect of influenza in health-care settings and for expanding influenza vaccine use (146,147).

Limited information is available regarding use of influenza vaccine among pregnant women. Among women aged 18--44 years without diabetes responding to the 2001 BRFSS, those who were pregnant were less likely to report influenza vaccination during the previous 12 months (13.7%) than those women who were not pregnant (16.8%); these differences were statistically significant (148). Only 13% of pregnant women reported vaccination according to 2004 NHIS data, excluding pregnant women who reported diabetes, heart disease, lung disease, and other selected high-risk conditions (CDC, unpublished data, 2006) (Table 3). These data indicate low compliance with the ACIP recommendations for pregnant women. In a study of influenza vaccine acceptance by pregnant women, 71% who were offered the vaccine chose to be vaccinated (149). However, a 1999 survey of obstetricians and gynecologists determined that only 39% administered influenza vaccine to obstetric patients, although 86% agreed that pregnant women's risk for influenza-related morbidity and mortality increases during the last two trimesters (150).

Data indicate that self-report of influenza vaccination among adults, compared with extraction from the medical record, is both a sensitive and specific source of information (151). Patient self-reports should be accepted as evidence of influenza vaccination in clinical practice (151). However, information on the validity of parents' reports of pediatric influenza vaccination is not yet available.

Recommendations for Using Inactivated and Live, Attenuated Influenza Vaccines

The inactivated influenza vaccine and LAIV can be used to reduce the risk for influenza virus infection and its complications. TIV is Food and Drug Administration (FDA)-approved for persons aged >6 months, including those with high-risk conditions, whereas LAIV is approved only for use among healthy persons aged 5--49 years (see Inactivated Influenza Vaccine Recommendations; and Live, Attenuated Influenza Vaccine Recommendations).

Target Groups for Vaccination

Annual influenza vaccination is recommended for the following groups:

Persons at Increased Risk for Complications

Vaccination with inactivated influenza vaccine is recommended for the following persons who are at increased risk for severe complications from influenza:

• children aged 6--23 months;
• children and adolescents (aged 6 months--18 years) who are receiving long-term aspirin therapy and, therefore, might be at risk for experiencing Reye syndrome after influenza virus infection;
• women who will be pregnant during the influenza season;
• adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including asthma (hypertension is not considered a high-risk condition);
• adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunodeficiency (including immunodeficiency caused by medications or by human immunodeficiency virus [HIV]);
• adults and children who have any condition (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration;
• residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions; and
• persons aged >65 years.