Clinical Syndromes, Laboratory Diagnosis and Treatment of Orthomyxoviruses

Clinical Syndromes

Depending on the degree of immunity to the infecting strain of virus and other factors, infection may range from asymptomatic to severe. Patients with underlying cardiorespiratory disease, people with immune deficiency (even that associated with pregnancy), the elderly, and smokers are more prone to have a severe case.

After an incubation period of 1 to 4 days, the “flu syndrome” begins with a brief prodrome of malaise and headache lasting a few hours. The prodrome is followed by the abrupt onset of fever, chills, severe myalgias, loss of appetite, weakness and fatigue, sore throat, and usually a nonproductive cough. The fever persists for 3 to 8 days, and unless a complication occurs, recovery is complete within 7 to 10 days. Influenza in young children (under 3 years) resembles other severe respiratory tract infections, causing bronchiolitis, croup, otitis media, vomiting, and abdominal pain, accompanied rarely by febrile convulsions (Table 1). Complications of influenza include bacterial pneumonia, myositis, and Reye syndrome. The central nervous system can also be involved. Influenza B disease is similar to influenza A disease.

Influenza may directly cause pneumonia, but it more commonly promotes a secondary bacterial superinfection that leads to bronchitis or pneumonia. The tissue damage caused by progressive influenza virus infection of alveoli can be extensive, leading to hypoxia and bilateral pneumonia. Secondary bacterial infection usually involves Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. In these infections, sputum usually is produced and becomes purulent.

Although the infection generally is limited to the lung, some strains of influenza can spread to other sites in certain people. For example, myositis (inflammation of muscle) may occur in children. Encephalopathy, although rare, may accompany an acute influenza illness and can be fatal. Postinfluenza encephalitis occurs 2 to 3 weeks after recovery from influenza. It is associated with evidence of inflammation but is rarely fatal.

Reye syndrome is an acute encephalitis that affects children and occurs after a variety of acute febrile viral infections, including varicella and influenza B and A diseases. Children given salicylates (aspirin) are at increased risk for this syndrome. In addition to encephalopathy, hepatic dysfunction is present. The mortality rate may be as high as 40%.

Laboratory Diagnosis

The diagnosis of influenza is usually based on the characteristic symptoms, the season, and the presence of the virus in the community. Laboratory methods that distinguish influenza from other respiratory viruses and identify its type and strain confirm the diagnosis (Table 2).

Influenza viruses are obtained from respiratory secretions. The virus is generally isolated in primary monkey kidney cell cultures or the Madin-Darby canine kidney cell line. Nonspecific cytopathologic effects are often difficult to distinguish but may be noted within as few as 2 days (average, 4 days). Before the cytopathologic effects develop, the addition of guinea pig erythrocytes may reveal hemadsorption (the adherence of these erythrocytes to HA-expressing infected cells). The addition of influenza virus-containing media to erythrocytes promotes the formation of a gel-like aggregate due to hemagglutination. Hemagglutination and hemadsorption are not specific to influenza viruses, however; parainfluenza and other viruses also exhibit these properties.

More rapid techniques detect and identify the influenza genome or antigens of the virus. Rapid antigen assays (less than 30 min) can detect and distinguish influenza A and B. Reverse transcriptase polymerase chain reaction (RT-PCR) using generic influenza primers can be used to detect and distinguish influenza A and B, and more specific primers can be used to distinguish the different strains, such as H5N1. Enzyme immunoassay or immunofluorescence can be used to detect viral antigen in exfoliated cells, respiratory secretions, or cell culture and are more sensitive assays. Immunofluorescence or inhibition of hemadsorption or hemagglutination (hemagglutination inhibition [HI]) with specific antibody can also detect and distinguish different influenza strains. Laboratory studies are primarily used for epidemiologic purposes.

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