Health Articles

Infection with influenza A or B virus, which causes an acute febrile illness of the respiratory tract.
Epidemiology and Pathogenesis
Infections wilh influenza viruses occur every year, either sporadically as local outbreaks or as a widespread epidemic. In the Northern Hemisphere epidemics occur almost exclusively during the winter months (December through April), and in the Southern Hemisphere they occur during (he summer months (May through September). Attack rates during such outbreaks may be as high as 10% lo 40% over 5 to 6 wk. The overall annual risk of dying of influenza is about 1/5,000 lo 1/10,000, although death rates are higher among elderly persons and among those with chronic diseases. Older persons, especially those with chronic medical conditions, account for at least 50% of all hospitalizations and 75% to 80% of all deaths attributed to influenza.
A unique feature of influenza virus is the frequency with which changes in antigenicity occur (principally involving the two external viral glycoproteins, hemagglutinin and neuraminidase). Changes in antigenicity occur almost annually with influenza A but less often with influenza B virus. Because of these alterations, variants of Ihe viruses develop to which the population at risk has little or no resistance, which helps explain why influenza epidemics continue. Antigenic variations are referred to as antigenic drift; major variations that herald pandemic influenza and create a virus to which the population has no immunity are called antigenic shift.
Influenza is spread by aerosol droplets expelled during coughing or sneezing. Low relative humidily and low environmental temperature foster the survival of airborne virus. After being deposited on respiratory tract epithelium, the virus attaches to its cellular receptor via hemagglutinin and penetrates columnar epithelial cells, unless il is prevented from doing so by secretory igA, by its attachment to nonspecific nucleoproteins, or by the action of the mucociliary apparatus. The virion then initiates a replication cycle within the cell, releasing virus for several hours before the cell dies. Released virus can infect nearby cells. Therefore, within a short period, many cells within the respiratory tract are either being infected, releasing virus, or dying.
The severiiy of illness correlates temporally with the amount of virus shed, suggesting that a major mechanism of illness is cell death resulting from viral replication. Shedding of virus precedes by 1 to 2 days the appearance of interferon in both nasal secretions and serum. The appearance of interferon coincides with an improvement in symptoms and a decrease in viral titers, suggesting that interferon may be active in the recovery process between the third and sixth days (before serum or secretory antibody is detected).
Symptoms and Signs
The clinical manifestations of influenza A and B viruses are similar. Influenza A is generally more severe, and five times as many persons with it require hospitalization compared to those wilh influenza B.
Many patients present wilh the classic flu-like syndrome, characterized by the abrupt onset of fever, chills, rigors, headache, myalgias, malaise, and anorexia. 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 h on the first day of illness, concurrently with the onset of systemic symptoms. The most troublesome initial symptoms are often headache and myalgias, which are related to the severity of the fever. Myalgias may involve the extremities or the long muscles of the back. Arthralgias, but not frank arthritis, are also common. 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 is a feature in < 5% of palients. Respiratory symptoms (ic, dry cough and 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 Ihe lower respiratory tract. Small, tender cervical lymph nodes develop in about 25% of patients.
On the second and third days of illness, the fever begins to diminish, along with reduction of syslcmic symptoms. As systemic symptoms and signs decline, respiratory complaints and findings, especially cough, become more apparent. The cough, which is nonproductive. may be accompanied by substernal discomfort or burning. Scattered wheezes or localized crackles are observed in < 20% of patients. Nasal obstruction and discharge can occur with pharyngeal pain and injection. These symptoms and signs usually persist for 3 to 4 days after the fever subsides, although full recovery can take 2 wk or more.
Complications
Numerous complications, especially pneumonia and severe bronchitis, can occur in elderly patients wilh influenza. The rate of occurrence is low in patients < 50 yr old but increases progressively with age and is high in those > 70yrold. This higher rate of severe pulmonary involvement may be attributed to the decline in cell-mediated immunily wilh aging.
Pneumonia may be a consequence of primary influenza viral infection or secondary bacterial infection (see PNEUMONIA in Ch. 46). Primary influenza pneumonia most often affects persons with cardiovascular disease, especially rheumatic heart disease with mitral stenosis, which is associated wilh increased pulmonary blood flow or pressure. Other chronic illnesses may increase risk as well. Healthy adults of any age may develop this deadly syndrome, although it occurs infrequently. The onset of influenza is usually typical, followed by rapid progression of fever, cough, dyspnea, and cyanosis; hemoptysis may occur. Auscultation reveals fine inspiratory crackles and inspiratory and expiratory wheezes. Chest x-rays usually show diffuse perihilar infiltrates. The mortality rate of primary influenza pneumonia is high.
Patients at risk for secondary bacterial pneumonia often have chronic pulmonary, cardiac, metabolic, or other diseases. A classic influenza illness is followed by a period of improvement (over 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 consolidalion found on physical examination. Chest x-rays show lobar or lobular infiltrates. Bacterial causes of pneumonia include the pneumococcus, Staphylococcus aureus. Hemophilus influenzae, and other grain-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, a toxic shock syndrome (probably from colonization of the trachea with S. aureus), Goodpasture’s syndrome, and CNS complications such as Guillain-Rarrc syndrome, transverse myelitis, and encephalitis. Anosmia and ageusia (loss of smell and taste) can develop and, although usually temporary, may last months.
Diagnosis
The local or state health department or the Centers for Disease Control and Prevention often will confirm that influenza virus is affecting a region or community. When this happens, mosl 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, 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 virus. Specimens are inoculated onto cell cultures and examined for cytopalhic effect or hemadsorption. Positive results appear in about 2h of cases within 3 days of testing and in the remainder of cases by 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 patienls at least 10 days after the onset of illness. Complement-fixing antibody tests are mosl commonly used for serologic diagnosis. A fourfold or grealer change in titer is considered diagnostic of infection.
Prophylaxis
Prevention of influenza is best accomplished by using inactivated virus vaccines (see also INFLUENZA VACCINE in Ch. 85). Antigenic drift makes disease prevention with vaccine a challenge. Each year the Public Health Service Advisory Committee on Immunization Practices makes recommendations regarding the composition of the influenza vaccine. Generally the vaccines contain both A and B inactivated viruses, usually the ones isolated from Ihe previous influenza season.
Persons at highest risk of infection—those with chronic diseases, all persons a 65 yr of age. and the medical personnel who provide their care—should be immunized annually with influenza vaccine. In addi-iion, immunization may be advisable for all persons who have extensive contact with elderly persons. Vaccination should be given in October, several weeks before the start of the influenza season. However, vaccination can be provided throughout the influenza season until the late winter. Efficacy rates vary from 67% to 92%; the vaccine is about 75% effective in reducing deaths from influenza in hospitalized, high-risk elderly persons. Diminished responses to the vaccine may be seen 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; vaccination is generally safe in persons who can eat eggs or egg-containing products. About 25% to 50% of patients experience some discomfort at the vaccine site 8 to 24 h after vaccination. About 1% to 2% of patients have fever or other systemic reactions. No further association of Guillain-Barre syndrome wilh influenza vaccination has been reported (the syndrome occurred sporadically in 1976 with the swine influenza immunization program). The vaccine cannot cause influenza or other respiratory infection.
Amantadine and rimantadine are approved for use as prophylactic agents against influenza; their efficacy is about 75% to 90%, similar to that of the influenza vaccine. In clinical studies, rimantadine is as effective as amantadine in preventing clinical influenza, and rimantadine has a lower incidence of side effects. The drugs are currently recommended as short-term (5 to 7 wk) prophylaxis during a presumed outbreak of influenza A for persons who did not receive the vaccine or for vaccinated persons (especially in a nursing home) who arc becoming ill at a high rate; they should be used for only 2 wk if vaccine is given simultaneously. The suggested dose for either amantadine or rimantadine is 100 mg once daily. Prophylaxis with amantadine or rimantadine may be particularly useful in nursing homes to protect un-vaccinated residents when others in the institution have become infected. In addition, the drugs may be used to supplement protection in patients expected (o have a poor antibody response to vaccination. Household contacts of a person infected with the virus may also be given prophylaxis, as may staff and patients in hospitals or institutions, to prevent an outbreak.
Treatment
The only drugs approved by the Kood and Drug Administration for the treatment of influenza A infection are amantadine and rimantadine. These drugs can reduce the symptoms and signs of influenza A infection and shorten its course by 1 or 2 days if given within 48 h of the onset of illness. Neither inhibits influenza B virus. For healthy elderly persons with normal renal function, the usual dose of amantadine is 200 mg initially, then 100 mg/day. The usual dose of rimantadine is 100 mg/day. 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 > 37.7″ C (> 100″ F) are given amantadine or rimantadine for 3 to 5 days.
Amantadine is associaled with minor, reversible CNS side effects such as nervousness, insomnia, dizziness, and difficulty in concentration. These side effects of amantadine therapy arc common in the elderly. Nonetheless, the prevention or relief of influenza symptoms is generally grealer than the toxicity of side effects, so thai patienls receive an overall net benefit with treatment. In patients with a known seizure disorder, seizures occur more often even when anticonvulsant therapy is maintained. Side effects occur less often with rimantadine than with amantadine, and rimantadine may eventually replace amantadine for treatment of uncomplicated influenza.
No conlrollcd trials have been conducted of amantadine or rimantadine in the treatment of influenza viral pneumonia; their use in this situation is based on anecdotal case reports and on data indicating that the drugs reduce peripheral airway resistance in uncomplicated influenza. Amantadine-resistant and rimantadine-resistant influenza A virus has been reported, allhough the long-term clinical significance of resistant virus has yet lo be determined.
Adjunctive therapy for influenza includes measures to provide symptomatic relief. Patients should remain at bed rest and receive additional fluids. Aspirin or acetaminophen is effeciivc in reducing fever. Patient? with proven or suspected bacterial pneumonia should receive antibiotics (sec PNEUMONIA in Ch. 46).

Infection with influenza A or B virus, which causes an acute febrile illness of the respiratory tract.
Epidemiology and Pathogenesis
Infections wilh influenza viruses occur every year, either sporadically as local outbreaks or as a widespread epidemic. In the Northern Hemisphere epidemics occur almost exclusively during the winter months (December through April), and in the Southern Hemisphere they occur during (he summer months (May through September). Attack rates during such outbreaks may be as high as 10% lo 40% over 5 to 6 wk. The overall annual risk of dying of influenza is about 1/5,000 lo 1/10,000, although death rates are higher among elderly persons and among those with chronic diseases. Older persons, especially those with chronic medical conditions, account for at least 50% of all hospitalizations and 75% to 80% of all deaths attributed to influenza.
A unique feature of influenza virus is the frequency with which changes in antigenicity occur (principally involving the two external viral glycoproteins, hemagglutinin and neuraminidase). Changes in antigenicity occur almost annually with influenza A but less often with influenza B virus. Because of these alterations, variants of Ihe viruses develop to which the population at risk has little or no resistance, which helps explain why influenza epidemics continue. Antigenic variations are referred to as antigenic drift; major variations that herald pandemic influenza and create a virus to which the population has no immunity are called antigenic shift.
Influenza is spread by aerosol droplets expelled during coughing or sneezing. Low relative humidily and low environmental temperature foster the survival of airborne virus. After being deposited on respiratory tract epithelium, the virus attaches to its cellular receptor via hemagglutinin and penetrates columnar epithelial cells, unless il is prevented from doing so by secretory igA, by its attachment to nonspecific nucleoproteins, or by the action of the mucociliary apparatus. The virion then initiates a replication cycle within the cell, releasing virus for several hours before the cell dies. Released virus can infect nearby cells. Therefore, within a short period, many cells within the respiratory tract are either being infected, releasing virus, or dying.
The severiiy of illness correlates temporally with the amount of virus shed, suggesting that a major mechanism of illness is cell death resulting from viral replication. Shedding of virus precedes by 1 to 2 days the appearance of interferon in both nasal secretions and serum. The appearance of interferon coincides with an improvement in symptoms and a decrease in viral titers, suggesting that interferon may be active in the recovery process between the third and sixth days (before serum or secretory antibody is detected).
Symptoms and Signs
The clinical manifestations of influenza A and B viruses are similar. Influenza A is generally more severe, and five times as many persons with it require hospitalization compared to those wilh influenza B.
Many patients present wilh the classic flu-like syndrome, characterized by the abrupt onset of fever, chills, rigors, headache, myalgias, malaise, and anorexia. 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 h on the first day of illness, concurrently with the onset of systemic symptoms. The most troublesome initial symptoms are often headache and myalgias, which are related to the severity of the fever. Myalgias may involve the extremities or the long muscles of the back. Arthralgias, but not frank arthritis, are also common. 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 is a feature in < 5% of palients. Respiratory symptoms (ic, dry cough and 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 Ihe lower respiratory tract. Small, tender cervical lymph nodes develop in about 25% of patients.
On the second and third days of illness, the fever begins to diminish, along with reduction of syslcmic symptoms. As systemic symptoms and signs decline, respiratory complaints and findings, especially cough, become more apparent. The cough, which is nonproductive. may be accompanied by substernal discomfort or burning. Scattered wheezes or localized crackles are observed in < 20% of patients. Nasal obstruction and discharge can occur with pharyngeal pain and injection. These symptoms and signs usually persist for 3 to 4 days after the fever subsides, although full recovery can take 2 wk or more.
Complications
Numerous complications, especially pneumonia and severe bronchitis, can occur in elderly patients wilh influenza. The rate of occurrence is low in patients < 50 yr old but increases progressively with age and is high in those > 70yrold. This higher rate of severe pulmonary involvement may be attributed to the decline in cell-mediated immunily wilh aging.
Pneumonia may be a consequence of primary influenza viral infection or secondary bacterial infection (see PNEUMONIA in Ch. 46). Primary influenza pneumonia most often affects persons with cardiovascular disease, especially rheumatic heart disease with mitral stenosis, which is associated wilh increased pulmonary blood flow or pressure. Other chronic illnesses may increase risk as well. Healthy adults of any age may develop this deadly syndrome, although it occurs infrequently. The onset of influenza is usually typical, followed by rapid progression of fever, cough, dyspnea, and cyanosis; hemoptysis may occur. Auscultation reveals fine inspiratory crackles and inspiratory and expiratory wheezes. Chest x-rays usually show diffuse perihilar infiltrates. The mortality rate of primary influenza pneumonia is high.
Patients at risk for secondary bacterial pneumonia often have chronic pulmonary, cardiac, metabolic, or other diseases. A classic influenza illness is followed by a period of improvement (over 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 consolidalion found on physical examination. Chest x-rays show lobar or lobular infiltrates. Bacterial causes of pneumonia include the pneumococcus, Staphylococcus aureus. Hemophilus influenzae, and other grain-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, a toxic shock syndrome (probably from colonization of the trachea with S. aureus), Goodpasture’s syndrome, and CNS complications such as Guillain-Rarrc syndrome, transverse myelitis, and encephalitis. Anosmia and ageusia (loss of smell and taste) can develop and, although usually temporary, may last months.
Diagnosis
The local or state health department or the Centers for Disease Control and Prevention often will confirm that influenza virus is affecting a region or community. When this happens, mosl 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, 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 virus. Specimens are inoculated onto cell cultures and examined for cytopalhic effect or hemadsorption. Positive results appear in about 2h of cases within 3 days of testing and in the remainder of cases by 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 patienls at least 10 days after the onset of illness. Complement-fixing antibody tests are mosl commonly used for serologic diagnosis. A fourfold or grealer change in titer is considered diagnostic of infection.
Prophylaxis
Prevention of influenza is best accomplished by using inactivated virus vaccines (see also INFLUENZA VACCINE in Ch. 85). Antigenic drift makes disease prevention with vaccine a challenge. Each year the Public Health Service Advisory Committee on Immunization Practices makes recommendations regarding the composition of the influenza vaccine. Generally the vaccines contain both A and B inactivated viruses, usually the ones isolated from Ihe previous influenza season.
Persons at highest risk of infection—those with chronic diseases, all persons a 65 yr of age. and the medical personnel who provide their care—should be immunized annually with influenza vaccine. In addi-iion, immunization may be advisable for all persons who have extensive contact with elderly persons. Vaccination should be given in October, several weeks before the start of the influenza season. However, vaccination can be provided throughout the influenza season until the late winter. Efficacy rates vary from 67% to 92%; the vaccine is about 75% effective in reducing deaths from influenza in hospitalized, high-risk elderly persons. Diminished responses to the vaccine may be seen 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; vaccination is generally safe in persons who can eat eggs or egg-containing products. About 25% to 50% of patients experience some discomfort at the vaccine site 8 to 24 h after vaccination. About 1% to 2% of patients have fever or other systemic reactions. No further association of Guillain-Barre syndrome wilh influenza vaccination has been reported (the syndrome occurred sporadically in 1976 with the swine influenza immunization program). The vaccine cannot cause influenza or other respiratory infection.
Amantadine and rimantadine are approved for use as prophylactic agents against influenza; their efficacy is about 75% to 90%, similar to that of the influenza vaccine. In clinical studies, rimantadine is as effective as amantadine in preventing clinical influenza, and rimantadine has a lower incidence of side effects. The drugs are currently recommended as short-term (5 to 7 wk) prophylaxis during a presumed outbreak of influenza A for persons who did not receive the vaccine or for vaccinated persons (especially in a nursing home) who arc becoming ill at a high rate; they should be used for only 2 wk if vaccine is given simultaneously. The suggested dose for either amantadine or rimantadine is 100 mg once daily. Prophylaxis with amantadine or rimantadine may be particularly useful in nursing homes to protect un-vaccinated residents when others in the institution have become infected. In addition, the drugs may be used to supplement protection in patients expected (o have a poor antibody response to vaccination. Household contacts of a person infected with the virus may also be given prophylaxis, as may staff and patients in hospitals or institutions, to prevent an outbreak.
Treatment
The only drugs approved by the Kood and Drug Administration for the treatment of influenza A infection are amantadine and rimantadine. These drugs can reduce the symptoms and signs of influenza A infection and shorten its course by 1 or 2 days if given within 48 h of the onset of illness. Neither inhibits influenza B virus. For healthy elderly persons with normal renal function, the usual dose of amantadine is 200 mg initially, then 100 mg/day. The usual dose of rimantadine is 100 mg/day. 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 > 37.7″ C (> 100″ F) are given amantadine or rimantadine for 3 to 5 days.
Amantadine is associaled with minor, reversible CNS side effects such as nervousness, insomnia, dizziness, and difficulty in concentration. These side effects of amantadine therapy arc common in the elderly. Nonetheless, the prevention or relief of influenza symptoms is generally grealer than the toxicity of side effects, so thai patienls receive an overall net benefit with treatment. In patients with a known seizure disorder, seizures occur more often even when anticonvulsant therapy is maintained. Side effects occur less often with rimantadine than with amantadine, and rimantadine may eventually replace amantadine for treatment of uncomplicated influenza.
No conlrollcd trials have been conducted of amantadine or rimantadine in the treatment of influenza viral pneumonia; their use in this situation is based on anecdotal case reports and on data indicating that the drugs reduce peripheral airway resistance in uncomplicated influenza. Amantadine-resistant and rimantadine-resistant influenza A virus has been reported, allhough the long-term clinical significance of resistant virus has yet lo be determined.
Adjunctive therapy for influenza includes measures to provide symptomatic relief. Patients should remain at bed rest and receive additional fluids. Aspirin or acetaminophen is effeciivc in reducing fever. Patient? with proven or suspected bacterial pneumonia should receive antibiotics (sec PNEUMONIA in Ch. 46).