Clinical Signs and Symptoms of Influenza

Influenza viruses are spread from person to person primarily through large-particle respiratory droplet transmission (e.g., when an infected person coughs or sneezes near a susceptible person) (14). Transmission via large-particle droplets requires close contact between source and recipient persons, because droplets do not remain suspended in the air and generally travel only a short distance (<1 meter) through the air. Contact with respiratory-droplet contaminated surfaces is another possible source of transmission. Airborne transmission (via small-particle residue [<5µm] of evaporated droplets that might remain suspended in the air for long periods of time) also is thought to be possible, although data supporting airborne transmission are limited (17-20). The typical incubation period for influenza is 1-4 days (average: 2 days) (21). Adults can be infectious from the day before symptoms begin through approximately 5 days after illness onset. Young children also might shed virus several days before illness onset, and children can be infectious for >10 days after onset of symptoms. Severely immunocompromised persons can shed virus for weeks or months (22-25).

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) (26). Among children, otitis media, nausea, and vomiting also are commonly reported with influenza illness (27-29). Uncomplicated influenza illness typically resolves after 3-7 days for the majority of persons, although cough and malaise can persist for >2 weeks. However, influenza virus infections can cause primary influenza viral pneumonia; exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease); lead to secondary bacterial pneumonia, sinusitis, or otitis; or contribute to coinfections with other viral or bacterial pathogens (30-32). Young children with influenza virus infection might have initial symptoms mimicking bacterial sepsis with high fevers (31-34), and febrile seizures have been reported in 6%-20% of children hospitalized with influenza virus infection (28,31,35). Population-based studies among hospitalized children with laboratory-confirmed influenza have demonstrated that although the majority of hospitalizations are brief (<2 days), 4%-11% of children hospitalized with laboratory-confirmed influenza required treatment in the intensive care unit, and 3% required mechanical ventilation (31,33). Among 1,308 hospitalized children in one study, 80% were aged <5 years, and 27% were aged <6 months (31). Influenza virus infection also has been uncommonly associated with encephalopathy, transverse myelitis, myositis, myocarditis, pericarditis, and Reye syndrome (28,30,36,37).

Respiratory illnesses caused by influenza virus infection are difficult to distinguish from illnesses caused by other respiratory pathogens on the basis of signs and symptoms alone. Sensitivity and predictive value of clinical definitions can vary, depending on the degree of circulation of other respiratory pathogens and the level of influenza activity (38). Among generally healthy older adolescents and adults living in areas with confirmed influenza virus circulation, estimates of the positive predictive value of a simple clinical definition of influenza (cough and fever) for laboratory-confirmed influenza infection have varied (range: 79%-88%) (39,40).

Young children are less likely to report typical influenza symptoms (e.g., fever and cough). In studies conducted among children aged 5-12 years, the positive predictive value of fever and cough together was 71%-83%, compared with 64% among children aged <5 years (41). In one large, population-based surveillance study in which all children with fever or symptoms of acute respiratory tract infection were tested for influenza, 70% of hospitalized children aged <6 months with laboratory-confirmed influenza were reported to have fever and cough, compared with 91% of hospitalized children aged 6 months-5 years. Among children with laboratory-confirmed influenza infections, only 28% of those hospitalized and 17% of those treated as outpatients had a discharge diagnosis of influenza (34). 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 (42). Among hospitalized older patients with chronic cardiopulmonary disease, a combination of fever, cough, and illness of <7 days was 53% predictive for confirmed influenza infection (43). The absence of symptoms of influenza-like illness (ILI) does not effectively rule out influenza; among hospitalized adults with laboratory-confirmed infection, only 51% had typical ILI symptoms of fever plus cough or sore throat (44). A study of vaccinated older persons with chronic lung disease reported that cough was not predictive of laboratory-confirmed influenza virus infection, although having both fever or feverishness and myalgia had a positive predictive value of 41% (45). These results highlight the challenges of identifying influenza illness in the absence of laboratory confirmation and indicate that the diagnosis of influenza should be considered in any patient with respiratory symptoms or fever during influenza season.

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