INFLUENZA : CLINICAL ASPECTS
As stated previously, influenza A and B viruses tend to cause the most severe illnesses, whereas influenza C seems to occur infrequently and generally causes milder disease. The typical acute influenzal syndrome is described here.
The incubation period is brief, lasting an average of 2 days. Onset is usually abrupt, with symptoms developing over a few hours. These include fever, myalgia, headache, and occasionally shaking chills. Within 6 to 12 hours, the illness reaches its maximum severity, and a dry, nonproductive cough develops. The acute findings persist, sometimes with wors-ening cough, for 3 to 5 days, followed by gradual improvement. By about 1 week after on-set, patients feel significantly better. However, fatigue, nonspecific weakness, and cough can remain frustrating lingering problems for an additional 2 to 6 weeks.
Occasionally, patients develop a progressive infection that involves the tracheo-bronchial tree and lungs. In these situations, pneumonia, which can be lethal, is the result. Other unusual acute manifestations of influenza include central nervous system (CNS) dysfunction, myositis, and myocarditis. In infants and children, a serious complication known as Reye’s syndrome may develop 2 to 12 days after onset of the infection. It is characterized by severe fatty infiltration of the liver and cerebral edema. This syndrome is associated not only with influenza viruses but with a wide variety of systemic viral ill-nesses. The risk is enhanced by exposure to salicylates, such as aspirin.
The most common and important complication of influenza virus infection is bacterial superinfection. Such infections usually involve the lung, but bacteremia with secondary seeding of distant sites can also occur. The superinfection, which can develop at any time in the acute or convalescent phase of the disease, is often heralded by an abrupt worsen-ing of the patient’s condition after initial stabilization. The bacteria most commonly in-volved include Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcusaureus.
In summary, there are essentially three ways in which influenza may cause death:
• Underlying disease with decompensation. Individuals with limited cardiovascularor pulmonary reserves can be further compromised by any respiratory infection. Thus, the elderly and those of any age with underlying chronic cardiac or pulmonary disease are at particular risk.
• Superinfection. Superinfection can lead to bacterial pneumonia and occasionallydisseminated bacterial infection.
• Direct rapid progression. Less commonly, progression of the viral infection can leadto overwhelming viral pneumonia with asphyxia.
During the acute phase of illness, influenza viruses can be readily isolated from respiratory tract specimens, such as nasopharyngeal and throat swabs. Most strains grow in primary monkey kidney cell cultures, and they can be detected by hemadsorption or hemagglutina-tion. Rapid diagnosis of infection is possible by direct immunofluorescence or immunoen-zymatic detection of viral antigen in epithelial cells or secretions from the respiratory tract. Serologic diagnosis is of considerable help epidemiologically and is usually made by demonstrating a fourfold or greater increase in hemagglutination inhibition antibody titers in acute and convalescent specimens collected 10 to 14 days apart.
The two basic approaches to management of influenzal disease are symptomatic care and anticipation of potential complications, particularly bacterial superinfection. Once the di- agnosis has been made, rest, adequate fluid intake, conservative use of analgesics for myalgia and headache, and antitussives for severe cough are commonly prescribed.
It must be emphasized that nonprescription drugs must be used with caution. This applies particularly to drugs containing salicylates given to children, because the risk of Reye’s syndrome must be considered.
Bacterial superinfection is often suggested by a rapid worsening of clinical symptoms after patients have initially stabilized. Antibiotic prophylaxis has not been shown to en-hance or diminish the likelihood of superinfection but can increase the risk of acquisition of more resistant bacterial flora in the respiratory tract and make the superinfection more difficult to treat. Ideally, physicians should instruct patients regarding the natural history of the influenza virus infection and be prepared to respond to bacterial complications, if they occur, with specific diagnosis and therapy.
When influenza A infection is proved or strongly suspected, 4 to 5 days of therapy with amantadine or rimantadine, two symmetric amines, may also be considered (Table 33–4). Such treatment has been shown to benefit some patients to a modest degree, as measured by reduction of number of days of confinement to bed, of fever, and of functional respira-tory impairment. However, these effects have been observed only when the drug is admin-istered early in the illness (within 12 to 24 hours of onset). The neuraminidase inhibitors (zanamivir or oseltamivir) have also proved beneficial, if begun early. They are also active against influenza B (see Table 33 – 4).
The best available method of control is by use of killed viral vaccines newly formulated each year to most closely match the influenza A and B antigenic subtypes currently caus-ing infections. These inactivated vaccines may contain whole virions or “split” subunits composed primarily of hemagglutinin antigens. They are commonly used, in two doses given 1 month apart, to immunize children who may not have been immunized previ-ously; among older children and adults, single annual doses are recommended just prior to influenza season. Vaccine efficacy is variable, and annual revaccination is necessary to ensure maximal protection. Used in this way, the virus vaccines may be 70 to 85% effec-tive. It is recommended that vaccination be directed primarily toward the elderly, individ-uals of all ages who are at high risk (eg, those with chronic lung or heart disease), and their close contacts, including medical personnel and household members. Live attenu-ated vaccines that are administered by nose drops are also being evaluated, and show con-siderable promise for the future.
Studies have shown that both amantadine and rimantadine are effective in short-term (several weeks) oral prophylaxis of influenza A infections. They act by blocking the ion channel of the viral M2 protein, resulting in interference with the key role for M2 protein in early virus uncoating. Later virion assembly may also be affected. However, these agents have side effects and are recommended only for high-risk patients until vaccine-induced immunity can be achieved. A typical example of their use would be during an epidemic in which an elderly, potentially susceptible patient may become exposed to in-fection within a defined period. Oral prophylaxis may be initiated concurrently with ad-ministration of a vaccine containing the most current antigens and continued for 2 weeks. The immunogenic effect of the vaccine should ensure continued protection. It must be emphasized that these drugs have been proven effective for influenza A virus infections only; they are useless in the management and prevention of infections caused by other types of influenza or by any other respiratory virus. Unfortunately, virus resistance to both drugs can readily develop in vitro or in vivo. A single amino acid substitution in the transmembrane portion of the M2 protein is all that is necessary for this to occur.
Zanamivir and oseltamivir, approved for use in 1999, both act by blocking the enzy-matically active neuraminidase glycoprotein present on the surfaces of influenza A and B viruses, thus limiting virus release from infected cells, and subsequent spread in the host. No viral resistance to these drugs has yet been noted (see Table 33–4).
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