AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Hakan Leblebicioglu, MD, Chairman, Professor, Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University Medical School, Turkey
Hakan Leblebicioglu is a member of the following medical societies: American Society for Microbiology
Coauthor(s):
Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Editors: David Jaimovich, MD, Chief Medical Officer, Joint Commission International and Joint Commission Resources; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine; Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine; Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
influenza, flu, grip, grippe, acute catarrhal fever, respiratory infection, upper respiratory tract infection, viral infection, severe acute respiratory syndrome, SARS, pharyngitis, rhinitis, cervical lymphadenopathy, conjunctivitis, coup, pneumonia, chronic respiratory disease, chronic cardiac disease, chronic renal failure, diabetes mellitus, immunosuppression
Background
Influenza is the one of the most significant acute upper respiratory tract infections. Influenza viruses cause a broad array of respiratory illnesses responsible for significant morbidity and mortality in children. Influenza viruses cause epidemic disease (influenza virus types A and B) and sporadic disease (type C) in humans.
Pathophysiology
Influenza is an acute infection of the respiratory tract in the nose, throat, and, sometimes, the lungs. Following respiratory transmission, the virus attaches to and penetrates respiratory epithelial cells in the trachea and bronchi. Viral replication occurs, which results in the destruction of the host cell. Viremia does not occur. The virus is shed in respiratory secretions for 5-10 days.
Influenza occurs as sporadic illness, epidemics, or pandemics. Epidemic disease occurs annually, especially in the winter months.
Influenza viruses cause global pandemics, in part because of the high degree of transmissibility and the emergence of an influenza virus with a major antigenic shift (major antigenic variations on the hemagglutinin surface protein) in a nonimmune population. The most recent pandemics included the 1889 pandemic, the 1918-1919 Spanish pandemic (influenza virus subtype H1), the 1957 pandemic (subtype H2N2), the 1968-1969 pandemic (Hong Kong subtype H3N2), and, to a lesser extent, the Russian pandemic in 1977 (subtype H1N1). Approximately 21 million persons died worldwide in the 1918-1919 influenza pandemic, with 549,000 deaths in the United States.
Frequency
United States
Approximately 250,000-500,000 new cases of influenza occur each year in the United States.
Mortality/Morbidity
Influenza viruses cause 20,000 deaths and 200,000 hospitalizations each year in the United States.
Race
No difference based on race has been identified.
Sex
No difference based on sex has been identified.
Age
The infection rate of influenza viruses is high in all age groups. The infection rate and the frequency of isolation of influenza viruses are highest in young children. The infection rate in healthy children is 10-30% annually.
History
- Typical symptoms of influenza begin 2-3 days after exposure to the virus.
- Influenza produces an acute febrile respiratory illness with cough, headache, and myalgia for 3-4 days, with symptoms that may persist for up to 2 weeks.
- Patients may present with sudden onset of the following:
- Subsequent respiratory symptoms include the following:
- Conjunctivitis, rhinitis, and GI tract symptoms are more common in infants and young children than in adults.
- In young infants, influenza may produce a sepsislike picture with shock; occasionally, influenza viruses can cause croup or pneumonia.
- Similar symptoms can be seen in close contacts or family members.
Causes
- Influenza is an acute infection caused by any of 3 types of viruses (A, B, C). Types A and B cause epidemic disease, and type C causes sporadic disease. Type A is the most common.
- Influenza is highly contagious. The virus is spread when an individual inhales infected air-borne droplets (following coughing or sneezing by an infected person) or comes in direct contact with an infected person's secretions (eg, kissing, sharing of handkerchiefs and other items, sharing of objects such as spoons and forks). Viruses may also be transmitted via touching of smooth surfaces, such as doorknobs, handles, and telephones.
- Influenza virus types A and B usually occur in the winter and spring.
- At-risk groups include elderly persons; individuals with chronic respiratory disease, chronic cardiac disease, chronic renal failure, diabetes mellitus, immunosuppression; and persons living in residential care homes and long-stay facilities.
- Severe acute respiratory syndrome (SARS)
- SARS is a serious, infectious, pulmonary illness that is spreading through many countries in Asia, with suspected cases in Europe, Australia, Canada, and the United States. The main symptoms include a high fever, cough, and shortness of breath or other breathing difficulties.
- On March 24, 2003, scientists at the Centers for Disease Control and Prevention (CDC) and in Hong Kong announced that a new coronavirus had been isolated from patients with SARS. Over the next 2 weeks, the machinery to discover and characterize the pathogen was set in full motion by scientists at the CDC and in 10 other World Health Organization (WHO)–collaborating laboratories. Coronavirus has not been proven to be the cause of SARS, but strong supportive evidence is accumulating. For more information, see the eMedicine article Severe Acute Respiratory Syndrome (SARS).
Chlamydial Infections
Mycoplasma Infections
Pharyngitis
Pneumonia
Q Fever
Respiratory Syncytial Virus Infection
Lab Studies
- Isolation of influenza viruses or detection of viral antigens in respiratory secretions (eg, throat swabs, nasopharyngeal washes, sputum) can be performed during acute influenza infection. Cultures should be obtained within 3 days of onset of illness.
- The type of influenza virus (A or B) may be determined by immunofluorescence or hemagglutination inhibition (HAI) techniques, and the hemagglutinin subtypes of influenza A virus (H1, H2, H3) may be identified using HAI with subtype-specific antisera.
- Complement-fixation (CF) and hemagglutination inhibition (HI) tests are the most common methods used to compare sera in persons with acute and convalescent infection, although these tests have low sensitivity and specificity. Rises in immunoglobulin (Ig) titer of at least 4 fold are considered diagnostic of infection. Significant rises as measured by enzyme-linked immunosorbent assay (ELISA) are diagnostic of acute infection.
- Viral antigens in respiratory secretions can be detected by immunofluorescence (IF) assay, time-resolved immunofluorescence assay (TRIFA), radioenzyme immunoassay, and ELISA. ELISA results can be obtained within 1 hour.
- Recently, rapid diagnostic testing for influenza A antigen has become available and should allow clinicians to assess the need for antiviral use in patients with influenza A infection in a timelier manner.
- Polymerase chain reaction (PCR) can be used to detect influenza virus RNA in respiratory secretions.
Imaging Studies
- Chest radiography may be necessary to exclude the diagnosis of pneumonia.
Medical Care
- Influenza symptoms may last longer than 1 week. Caregivers can relieve and soothe children's aches and pains with basic supportive care.
- Acetaminophen may be administered for fever and relief of other symptomatology. (Caution: In children <16 y who have symptoms of influenza infection or colds, aspirin is not recommended because of an association with Reye syndrome.)
- Use cough suppressants and expectorants to treat the cough. Steam inhalations may also be useful. If dehydration occurs, administration of oral or intravenous fluids is indicated.
Diet
- No special diet is indicated for influenza.
Activity
- Adequate rest is recommended.
The following 4 antiviral agents are approved for preventing or treating influenza: amantadine, rimantadine, zanamivir, and oseltamivir.
Amantadine and rimantadine are effective against type A influenza virus only. They are approved by the US Food and Drug Administration (FDA) for influenza type A prophylaxis in patients older than 1 year. Amantadine is also FDA-approved for treatment in children. Since the 2005-2006 influenza season, amantadine and rimantadine are no longer recommended by the CDC because of resistance. Laboratory testing by the CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs. Zanamivir and oseltamivir are members of a new class of drugs termed neuraminidase inhibitors and are active against both influenza virus type A and type B. Zanamivir is provided as a dry powder that is administered by inhalation. It is approved for the treatment of uncomplicated acute influenza A or B in persons aged 7 years and older who have been symptomatic for no more than 2 days. Oseltamivir is approved for oral administration in persons older than 1 year with influenza A or B who have been symptomatic for no more than 2 days. Neither zanamivir nor oseltamivir is approved for prophylaxis of influenza infection. Treatment of influenza A virus illness should be started as soon as possible, preferably within 24-48 hours after onset of signs and symptoms, and should be continued for 24-48 hours after the disappearance of signs and symptoms.
Drug Category: Antiviral agents
Use of influenza-specific antiviral drugs for chemoprophylaxis or treatment of influenza is an important adjunct to vaccine, particularly for controlling outbreaks in closed populations.
| Drug Name | Amantadine (Symmetrel) |
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| Description | Prevents penetration of virus into host by inhibiting uncoating of influenza A. No longer recommended by the CDC because of resistance. Laboratory testing by the CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs. |
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| Adult Dose | Prophylaxis or treatment:
200 mg/d PO in 1-2 divided doses |
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| Pediatric Dose | Prophylaxis or treatment:
<1 year: Not established
1-9 years: 5-9 mg/kg/d qd or divided bid; not to exceed 150 mg/d
10-12 years: 100-200 mg/d qd or divided bid
>12 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Drugs with anticholinergic or CNS stimulant activity increase amantadine toxicity; concurrent administration of hydrochlorothiazide plus triamterene with amantadine may increase plasma concentrations of amantadine |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, and seizures and in patients receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not discontinue abruptly |
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| Drug Name | Rimantadine (Flumadine) |
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| Description | Inhibits viral replication of influenza A virus subtypes H1N1, H2N2, and H3N2. Prevents penetration of the virus into the host by inhibiting uncoating of influenza A. No longer recommended by the CDC because of resistance. Laboratory testing by the CDC on the predominant strain of influenza (H3N2) currently circulating in the United States shows that it is resistant to these drugs. |
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| Adult Dose | 100 mg PO bid; decrease dose to 100 mg/d PO with severe renal or hepatic disease or in elderly persons |
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| Pediatric Dose | Prophylaxis or treatment:
<40 kg: 5 mg/kg/d PO; not to exceed 150 mg/d
>40 kg: Administer as in adults |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Acetaminophen and aspirin reduce rimantadine levels when taken concurrently; cimetidine increases rimantadine plasma levels when taken concomitantly |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Caution in hepatic impairment |
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| Drug Name | Oseltamivir (Tamiflu) |
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| Description | Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against influenza virus types A and B. Available as cap and an PO susp. |
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| Adult Dose | Acute illness: 75 mg PO bid for 5 d
Prophylaxis: 75 mg/d PO for 10 d |
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| Pediatric Dose | Acute illness:
>1 year:
<15 kg: 2 mg/kg PO bid for 5 d; not to exceed 30 mg PO bid
15-23 kg: 45 mg PO bid for 5 d
24-40 kg: 60 mg PO bid for 5 d
>40 kg: Administer as in adults
Prophylaxis:
>1 year:
<15 kg: 30 mg PO qd for 10 d
15-23 kg: 45 mg PO qd for 10 d
24-40 kg: 60 mg PO qd for 10 d
>40 kg: Administer as in adults
|
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid may decrease clearance |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Caution in renal impairment (decrease dose if CrCl <30 mL/min), chronic cardiac or respiratory disease, and breastfeeding; may cause nausea or vomiting |
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| Drug Name | Zanamivir (Relenza) |
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| Description | Inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Effective against both influenza types A and B. To be inhaled through a Diskhaler PO inhalation device. Circular foil disks containing 5-mg blisters of drug are inserted into a supplied inhalation device. |
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| Adult Dose | Treatment: 2 inhalations (10 mg) PO bid for 5 d; initiate within 2 d of symptom onset
Prophylaxis: 2 inhalations (10 mg) PO qd for 10 d; initiate within 36 h of exposure
Note: One 5-mg blister per inhalation; 10-mg dose equals two 5-mg blisters |
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| Pediatric Dose | Treatment:
<7 years: Not established
>7 years: Administer as in adults
Prophylaxis:
<5 years: Not established
>5 years: Administer as in adults |
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| Contraindications | Documented hypersensitivity; obstructive airway disease |
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| Interactions | None reported |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Monitor respiratory status; may cause bronchospasm; contraindicated with asthma or COPD; caution in breastfeeding |
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Deterrence/Prevention
- Handwashing with soap and water is the most appropriate way to prevent infection by an influenza virus.
- Touching of eyes or nose before washing hands should be avoided.
- Personal items should not be shared with another person during an influenza outbreak.
- Chemoprophylaxis is a less desirable alternative and is only effective against influenza A virus.
- Influenza vaccination in targeted high-risk populations is the best means of preventing severe disease caused by influenza virus.
- Vaccines made using inactivated influenza virus provide 60-90% protection against influenza when the vaccine matches the epidemic strain.
- The antigenic composition is reviewed annually so that the current vaccine contains the most recently circulating strains, usually one or more subtypes of influenza A virus and a subtype of influenza B virus.
- Vaccine efficacy for preventing infection in elderly persons is 30-40%. Efficacy in preventing hospitalization for pneumonia and influenza is 50-60% in elderly persons living in nursing homes and 30-70% in elderly persons living outside of nursing homes. Efficacy in preventing death in elderly patients who live in nursing homes is 80%.
- Indications for influenza vaccine include the following:
- Persons aged 65 years and older (and recommended for those aged 50-64 y)
- Residents of nursing homes and other long-term–care facilities
- Patients with chronic pulmonary (eg, asthma) or cardiac disorders (except hypertension)
- Patients with chronic metabolic disease (eg, diabetes), renal dysfunction, hemoglobinopathies, or immunosuppression (eg, human immunodeficiency virus [HIV])
- Children and teenagers (6 mo to 18 y) with long-term use of aspirin1, 2
- Persons who have any condition (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that may compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration
- Pregnant women who will be in their second or third trimester during influenza season
- Physicians, nurses, and other health care providers
- Employees of nursing homes and long-term care facilities
- Providers of home care to persons at high risk
- Household members (eg, children aged <5 years) of persons at high risk
- Providers of essential community services (eg, police, fire)
- International travelers
- Students and dormitory residents
- Anyone wishing to reduce risk of influenza
- The CDC recommends that the following groups receive priority for inactivated influenza vaccine:
- Persons aged 50 years and older
- Residents of long-term–care facilities
- Persons aged 2-64 years with comorbid conditions
- Children aged 6 months to 4 years (59 months)1, 2
- Women who will be pregnant during the influenza season
- Health care providers who provide direct patient care
- Household contacts and out-of-home caregivers of children younger than 6 months
- Administration of influenza vaccine includes the following:
- For adults and older children, the recommended site of vaccination is the deltoid muscle.
- The preferred site for infants and young children is the anterolateral aspect of the thigh.
- Influenza vaccine should be administered during the autumn season.
- Vaccination is recommended in children aged 6 months or older.
- Two doses administered at least 1 month apart are recommended in children 6 months to 8 years who are receiving influenza vaccine for the first time. Other children or adults may be vaccinated with one shot.
- Annual immunization is recommended because of declining immunity during the year after immunization and because, in most years, at least one of the antigens is changed in the vaccine to increase the antigenic similarity between the vaccine and circulating strains. The optimal time for influenza vaccination is usually between October and November.
- Influenza vaccine should not be administered to persons known to have severe anaphylactic hypersensitivity to egg protein or to other components of the influenza vaccine.
- The presence of minor illnesses with or without fever is not a contraindication to the use of influenza vaccine.
- Influenza vaccine may be administered with pneumococcal vaccine and with other routine vaccinations of childhood.
- Influenza vaccine is also available as a nasal spray (FluMist) for healthy children aged 2 years or older, adolescents, and adults aged 49 years or younger. Children aged 2-8 years who have not previously received influenza vaccine as a nasal spray require 2 doses at least 1 month apart. Those who only received 1 dose in their first year of vaccination should receive 2 doses in the following year. Children who take aspirin, have asthma, or have had a wheezing episode in the preceding 12 months should not receive the FluMist vaccine.
Complications
- Primary influenza viral pneumonia
- Secondary bacterial pneumonia
- Croup
- Exacerbation of chronic pulmonary disease
- Myositis
- Myocarditis
- Toxic shock syndrome
- Guillain-Barré syndrome
- Reye syndrome
Prognosis
- The prognosis for recovery is excellent, although full return to normal levels of activity and freedom from cough usually requires weeks rather than days.
Patient Education
Special Concerns
- In children younger than 16 years who have symptoms of influenza or colds, aspirin is not recommended because of an association with Reye syndrome.
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Influenza excerpt Article Last Updated: Oct 7, 2008
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