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New Treatments for Influenza

Influenza is a common midwinter respiratory illness caused by members of the viral family Orthomyxoviridae. The primary etiologic agents are influenza A and B. Disease is spread by respiratory droplet or direct contact; in adults and older children it is characterized by an abrupt onset of fever, cough, sore throat, myalgias, and headache. Younger children exhibit less localized findings such as high fever and abdominal pain. In all patients, complications include viral or bacterial pneumonia (concurrent or subsequent); children frequently develop croup, otitis media, and myositis (the latter particularly after type B infection). The incidence of Reye syndrome following influenza has declined remarkably in the past decade, possibly due to decreased aspirin use by children. Several diagnostic tests using immunofluorescent enzyme-linked immunoabsorbent (ELISA) assays assist clinicians in rapid diagnosis.

Influenza viruses possess two types of surface glycoproteins, a hemagglutinin (H) and a neuraminidase (N), which are critically important in the human immune response. After infection, patients develop increases in serum antibody to these proteins, which correlate with protection to that particular isolate of influenza. Over time, influenza A and B undergo minor antigenic changes known as "drift," which coupled with waning immunity, eventually allow for reinfection of segments of the population. Influenza A periodically undergoes major "shifts" or exchanges of H and/or N antigens, possibly by gene acquisition from animal or avian influenza viruses. When this occurs, large portions of the population are naive to this new or resurgent combination, which may lead to worldwide pandemics, such as occurred in 1968 when the H2N2 subtype was superseded by the emergence of an H3N2 (Hong Kong) subtype.

Inactivated influenza vaccine is approximately 70% effective in preventing disease. The vaccine is revised annually to contain representative circulating isolates, which in recent years have included H3N2 and H1N1 type A isolates as well as a representative type B isolate. The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend annual immunization of all persons 6 months of age or older who are at increased risk for influenza-related complications, such as patients who have cardiac disease, asthma, cystic fibrosis, bronchopulmonary dysplasia, diabetes, renal dysfunction, or hemoglobinopathies; chronic states of immunosuppression; stable conditions at least 1 year after bone marrow transplant; and those receiving prolonged aspirin therapy. In addition, household contacts of these high-risk children as well as all associated medical care personnel should receive annual influenza immunizations. Children should receive only the more purified subvirion or surface antigen preparations, which may decrease the incidence of such minor side effects as fever, malaise, and myalgias. Fortunately, in recent years, use of influenza vaccine has not been associated with the increased incidence of Guillian-Barre syndrome that was seen after the mass swine influenza.

We can continue to expect annual flu epidemics. Particularly virulent strains have resulted in pandemics four times this century (last in 1977). Despite advances in chemoprophylaxis and therapy, yearly vaccination of high-risk persons continues to be the most effective strategy for influenza.