Influenza

Infection with influenza A or B virus, which causes an acute febrile illness of the respiratory tract.

Infections with influenza viruses occur every year, either sporadically as local outbreaks or as a widespread epidemic. In the Northern Hemisphere, epidemics occur almost exclusively during December through April; in the Southern Hemisphere, during May through September. Attack rates during such outbreaks may be as high as 10 to 40% over 5 to 6 weeks. The overall annual risk of dying of influenza is about 1/5,000 to 1/10,000; death rates are higher among the elderly and among those with chronic diseases. Elderly persons, especially those with chronic medical conditions, account for at least 50% of all hospitalizations and for > 80% of all deaths attributed to influenza.

Influenza is transmitted via aerosol droplets expelled during coughing or sneezing. Low relative humidity and low environmental temperature foster the survival of airborne virus.

Symptoms and Signs

The clinical manifestations of influenza A and B viruses are similar. Influenza A is generally more severe and requires hospitalization much more frequently.

The classic syndrome is characterized by the abrupt onset of fever, chills, rigors, headache, myalgias, malaise, anorexia, sore throat, and a nonproductive cough. Early in the course of illness, the patient appears to be in a toxic condition: the face is flushed, and the skin is hot and moist. Prostration may occur in severe cases.

Fever is a consistent feature of influenza infection. Among elderly persons, fever is common, although the temperature may not rise as high as it does in children and young adults. The temperature usually rises rapidly within 12 hours on the first day of illness, concurrent with the onset of systemic symptoms. Myalgias may involve the extremities or the long muscles of the back. Lateral gaze may elicit pain in the eye muscles; photophobia and other ocular symptoms (including injected, watery, and burning eyes) occur in up to 20% of patients. Diarrhea occurs in < 5% of patients. Respiratory symptoms (ie, dry cough, a clear nasal discharge) are usually present at the onset of illness but are overshadowed by nonrespiratory symptoms. Nasal obstruction, hoarseness, and a dry or sore throat may also occur. Hyperemia of the mucous membranes of the nose and throat develops, but exudate generally does not. Most persons with influenza develop bronchitis without other involvement of the lower respiratory tract. Small, tender cervical lymph nodes develop in about 25% of patients.

On the 2nd and 3rd days of illness, as systemic symptoms and signs decline, respiratory symptoms and signs, especially cough, become more apparent. Scattered wheezes or localized crackles are observed in < 20% of patients. Elderly patients are often left extremely weak even after other symptoms resolve. Full recovery can take >= 2 weeks.

Complications

Pneumonia and severe bronchitis commonly accompany influenza in the elderly; the rate increases progressively in persons > 50 and is high in persons > 70. Pneumonia may be due to primary influenza viral infection or to secondary bacterial infection.

Primary influenza pneumonia most often affects persons with cardiovascular disease, especially rheumatic heart disease with mitral stenosis. Other chronic illnesses may increase risk as well. Fever, cough, dyspnea, cyanosis, and hemoptysis may occur. Auscultation reveals fine inspiratory crackles and inspiratory and expiratory wheezes. Chest x-rays usually show diffuse perihilar infiltrates. The mortality rate associated with primary influenza pneumonia is high.

Patients at risk of secondary bacterial pneumonia include those with chronic pulmonary, cardiac, metabolic, or other chronic diseases. A classic influenza illness is followed by a period of improvement (4 to 14 days) before the clinical course worsens and symptoms and signs of bacterial pneumonia appear. The syndrome consists of fever, productive cough, and an area of decreased breath sounds and dullness to percussion. Chest x-rays show lobar or lobular infiltrates. Bacterial causes of pneumonia include pneumococcus, Staphylococcus aureus, H. influenzae, and other gram-positive and gram-negative organisms.

Many nonpulmonary complications have been described in patients with influenza, including myositis (sometimes with myoglobinuria and renal failure), myocarditis and pericarditis, toxic shock syndrome (probably from colonization of the trachea with S. aureus), Goodpasture's syndrome, and central nervous system complications, such as Guillain-Barré syndrome, transverse myelitis, and encephalitis. Anosmia and ageusia (loss of smell and taste) can develop and, although usually temporary, may last for months.

Diagnosis

The local or state health department or the CDC often can confirm that influenza virus is affecting a region or community. In such cases, most persons with fever, muscle aches, and cough are likely to have influenza.

Although rarely indicated, specific diagnostic procedures can be used to detect virus or viral antigens in respiratory secretions. Early in the course of illness, the virus can be isolated from nasal or throat swab specimens, nasal washes, or sputum; bronchoalveolar lavage and lung tissue specimens can also be used to isolate the virus. Positive results appear in about two thirds of cases within 3 days of testing and in the remainder of cases in 5 to 7 days. Virus can also be cultured by the inoculation of embryonated hens' eggs.

Serologic tests, although sensitive and specific, do not yield data within a clinically relevant time because sera must be obtained from convalescing patients at least 10 days after the onset of illness.

Prevention

Vaccination: Prevention of influenza is best accomplished by using inactivated virus vaccines. All persons >= 65 and the medical personnel who care for them should receive the influenza vaccine annually. In addition, annual vaccination may be advisable for all persons who have extensive contact with elderly persons. Vaccination should be given several weeks before the start of the influenza season. In the USA, vaccination should be given in October, although it can be given throughout the influenza season until the late winter.

Efficacy rates for preventing influenza illness in the frail elderly are 30 to 70%; however, the vaccine is 50 to 60% effective in preventing hospitalization and pneumonia and about 75% effective in reducing deaths from influenza in hospitalized high-risk elderly patients. Diminished responses to the vaccine may occur in very elderly persons and in those who have renal failure or who are immunocompromised.

The only contraindication to vaccination is hypersensitivity to hens' eggs. About 25 to 50% of patients have some discomfort at the vaccine site 8 to 24 hours after vaccination. About 1 to 2% of patients have fever or other systemic reactions. The vaccine cannot cause influenza or other respiratory infection.

Antiviral drugs: The new neuraminidase inhibitors oseltamivir and zanamivir appear effective in the prevention of influenza A and B. Amantadine and rimantadine provide prophylaxis against influenza A; their efficacy is about 75 to 90%. Rimantadine is as effective as amantadine in preventing clinical influenza and has a lower incidence of adverse effects. It is recommended for short-term (5 to 7 weeks) prophylaxis during a presumed outbreak of influenza A for unvaccinated persons and for vaccinated persons (especially those in a long-term care facility) who are becoming ill at a high rate. Prophylaxis may be particularly useful for unvaccinated residents of long-term care facilities. In addition, amantadine and rimantadine may be used to supplement protection in patients expected to have a poor antibody response to vaccination. Household contacts of a person infected with the virus may also be given prophylaxis, as may staff members and patients in hospitals or institutions, to prevent an outbreak. Use of these drugs should not exceed 2 weeks if vaccine is given simultaneously. The suggested dose for rimantadine for elderly persons without renal failure is 100 mg po once daily.

Treatment

Oseltamivir and zanamivir are effective for influenza A and B. These drugs must be given within 48 hours of symptom onset. They reduce symptom duration, including fever, by about 1 to 1.5 days, and substantially decrease viral shedding. These drugs lack CNS toxicity; however, oseltamivir may have GI adverse effects.

Amantadine and rimantadine can reduce the symptoms and signs of influenza A infection and shorten its course by 1 or 2 days if given within 48 hours of symptom onset. Neither drug inhibits influenza B virus. For healthy elderly persons with normal renal function, the usual dose of rimantadine is 100 mg/day po. When the index of suspicion is high (ie, during the winter months and when influenza has been reported in or near the community), patients who have an influenza-like illness and temperature > 37.8° C (> 100° F) are given rimantadine for 3 to 5 days even if they have been vaccinated.

Rimantadine is generally better tolerated than amantadine. Amantadine is associated with minor reversible CNS adverse effects, such as nervousness, insomnia, dizziness, and difficulty concentrating; such effects are common in the elderly, although they can occur with rimantadine as well. In patients with a known seizure disorder, seizures occur more often even when anticonvulsant therapy is maintained. In elderly persons with severe liver dysfunction, the apparent clearance of rimantadine is reduced by 50% compared with that of elderly patients with normal liver function; thus, this drug must be administered cautiously. In influenza viral pneumonia, these drugs may reduce peripheral airway resistance.

Adjunctive therapy for influenza includes measures to provide symptomatic relief. Patients should remain on bed rest and receive additional fluids. Aspirin or acetaminophen is effective in reducing fever.

Patient and Caregiver Issues

Elderly patients without comorbidity can be treated as outpatients, because the treatment of influenza is largely supportive. However, frail and bedridden elderly patients must be closely monitored for evidence of superimposed bacterial pneumonia. Caregivers should maintain communication with the physician in such cases.

In cases of poor family support, home health care is generally an effective alternative to institutionalized care. Because severe influenza can be a terminal disease, issues regarding advance directives must be addressed.