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

Nicole M. Smith, PhD; Joseph S. Bresee, MD; David K. Shay, MD; Timothy M. Uyeki, MD; Nancy J. Cox, PhD; Raymond A. Strikas, MD


Morbidity and Mortality Weekly Report. 2006;55(27):1-41. 

In This Article

Influenza and Its Burden

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.

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.[29,30,31,32]

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.[34,35,36] 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.

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.[1,6,8,48,49,50,51,52,53,54,55,56] 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.[57,58,59,60] 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]


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