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Clinical Signs and Symptoms of Influenza
Influenza viruses are spread from person to person primarily through the coughing and sneezing of infected persons. The incubation period for influenza is 1–4 days, with an average of 2 days. Adults typically are infectious from the day before symptoms begin through approximately 5 days after illness onset. Children can be infectious for >10 days, and young children can shed virus for <6 days before their illness onset. Severely immunocompromised persons can shed virus for weeks or months.
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). Among children, otitis media, nausea, and vomiting are also commonly reported with influenza illness. Respiratory illness caused by influenza is difficult to distinguish from illness caused by other respiratory pathogens on the basis of symptoms alone (see Role of Laboratory Diagnosis). Reported sensitivities and specificities of clinical definitions for influenza-like illness in studies primarily among adults that include fever and cough have ranged from 63% to 78% and 55% to 71%, respectively, compared with viral culture. 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. A study among older nonhospitalized patients determined that symptoms of fever, cough, and acute onset had a positive predictive value of 30% for influenza, 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. However, a study among vaccinated older persons with chronic lung disease reported that cough was not predictive of influenza infection, although having a fever or feverishness was 68% sensitive and 54% specific for influenza infection.
Influenza illness typically resolves after a limited number of days for the majority of persons, although cough and malaise can persist for >2 weeks. 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. Young children with influenza infection can have initial symptoms mimicking bacterial sepsis with high fevers, and <20% of children hospitalized with influenza can have febrile seizures. Influenza infection has also been associated with encephalopathy, transverse myelitis, Reye syndrome, myositis, myocarditis, and pericarditis.
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 (1,6,8,45–50). Estimated rates of influenza-associated hospitalizations have varied substantially by age group in studies conducted during different influenza epidemics (Table 1).
Among children aged 0–4 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. Within the 0–4 year age group, hospitalization rates are highest among children aged 0–1 years and are comparable to rates reported among persons >65 years (Table 1).
During influenza epidemics from 1969–70 through 1994–95, the estimated overall number of influenza-associated hospitalizations in the United States ranged from approximately 16,000 to 220,000/epidemic. An average of approximately 114,000 influenza-related excess hospitalizations occurred per year, with 57% of all hospitalizations occurring among persons aged <65 years. Since the 1968 influenza A (H3N2) virus pandemic, the greatest numbers of influenza-associated hospitalizations have occurred during epidemics caused by type A (H3N2) viruses, with an estimated average of 142,000 influenza-associated hospitalizations per year.
Influenza-related deaths can result from pneumonia as well as from exacerbations of cardiopulmonary conditions and other chronic diseases. Older adults account for >90% of deaths attributed to pneumonia and influenza. In a recent study of influenza epidemics, 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. 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 might be increasing in part because the number of older persons is increasing. In addition, influenza seasons in which influenza A (H3N2) viruses predominate are associated with higher mortality; influenza A (H3N2) viruses predominated in 90% of influenza seasons during 1990–1999, compared with 57% of seasons during 1976–1990.
Deaths from influenza are uncommon among children with and without high-risk conditions, but do occur. A study that modeled influenza-related deaths estimated that an average of 92 deaths occurred among children aged <5 years annually during the 1990's compared with 35,274 deaths among adults aged >50 years. Preliminary reports of laboratory- confirmed pediatric deaths during the 2003–04 influenza season indicated that among these 143 influenza-related deaths (as of April 10, 2004), 58 (41%) were aged <2 years and, of those aged 2–17 years, 65 (45%) did not have an underlying medical condition traditionally considered to place a person at risk for influenza-related complications (unpublished data, CDC National Center for Infectious Diseases, 2004). Further information is needed regarding the risk of severe influenza-complications and optimal strategies for minimizing severe disease and death among children.
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