Updated: Aug 11, 2009
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.
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.
If swine influenza (swine flu) is suspected, clinicians should obtain a respiratory swab for swine influenza (swine flu) testing and place it in a refrigerator (not a freezer). Once collected, the clinician should contact their state or local health department to facilitate transport and timely diagnosis at a state public health laboratory.5
The new virus is resistant to the antiviral agents amantadine and rimantadine but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). Initiation of antiviral agents within 48 hours of symptom onset is imperative to provide treatment efficacy against influenza virus. The usual vaccine for influenza administered at the beginning of the influenza season is not effective for this viral strain.
Initial symptoms of swine influenza (swine flu) include high fever, myalgias, rhinorrhea, and sore throat. Nausea, diarrhea, and vomiting have also been reported. Infection control precautions (ie, handwashing, covering mouth with tissue when sneezing or coughing) are encouraged. If suspected swine influenza occurs, isolation is recommended for infected individuals and household contacts. For more information, see updated information from the CDC. For guidance in managing suspected cases, see Medscape's H1N1 influenza algorithm adaptation.
Approximately 250,000-500,000 new cases of influenza occur each year in the United States.
Influenza viruses cause 20,000 deaths and 200,000 hospitalizations each year in the United States.
No difference based on race has been identified.
No difference based on sex has been identified.
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.
Chlamydial Infections
Mycoplasma Infections
Pharyngitis
Pneumonia
Q Fever
Respiratory Syncytial Virus Infection
The following 4 antiviral agents are approved for preventing or treating influenza: amantadine, rimantadine, zanamivir, and oseltamivir.6
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.
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.
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.
Prophylaxis or treatment:
200 mg/d PO in 1-2 divided doses
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
Drugs with anticholinergic or CNS stimulant activity increase amantadine toxicity; concurrent administration of hydrochlorothiazide plus triamterene with amantadine may increase plasma concentrations of amantadine
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
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.
100 mg PO bid; decrease dose to 100 mg/d PO with severe renal or hepatic disease or in elderly persons
Prophylaxis or treatment:
<40 kg: 5 mg/kg/d PO; not to exceed 150 mg/d
>40 kg: Administer as in adults
Acetaminophen and aspirin reduce rimantadine levels when taken concurrently; cimetidine increases rimantadine plasma levels when taken concomitantly
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Caution in hepatic impairment
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.
Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009 influenza season. The CDC has issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data from a limited number of states indicate the prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu) is high. Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. A second-line alternative is a combination of oseltamivir plus rimantadine, rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.
Acute illness: 75 mg PO bid for 5 d
Prophylaxis: 75 mg/d PO for 10 d
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
Probenecid may decrease clearance
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Caution in renal impairment (decrease dose if CrCl <30 mL/min), chronic cardiac or respiratory disease, and breastfeeding; may cause nausea or vomiting
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.
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
Treatment:
<7 years: Not established
>7 years: Administer as in adults
Prophylaxis:
<5 years: Not established
>5 years: Administer as in adults
None reported
Documented hypersensitivity; obstructive airway disease
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Monitor respiratory status; may cause bronchospasm; contraindicated with asthma or COPD; caution in breastfeeding
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Swine Influenza (Flu). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/swineflu/. Accessed April 27, 2009.
Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans. N Engl J Med. Jun 3 2009;[Medline].
Update: Novel Influenza A (H1N1) Virus Infection-- Worldwide, May 6, 2009. MMWR. May 2009;58:453-8.
Guidance for Clinicians and Public Health Professionals. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/swineflu/guidance/. Accessed April 27, 2009.
[Best Evidence] Tappenden P, Jackson R, Cooper K, et al. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technol Assess. Feb 2009;13(11):iii, ix-xii, 1-246. [Medline].
Fiore AE, Shay DK, Broder K, et al. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep. Aug 8 2008;57:1-60. [Medline].
[Guideline] Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. Jul 31 2009;58:1-52. [Medline]. [Full Text].
American Academy of Pediatrics Committee on Infectious Diseases. Prevention of influenza: recommendations for influenza immunization of children, 2007-2008. Pediatrics. Apr 2008;121(4):e1016-31. [Medline].
ALA Asthma Clinical Research Center. The safety of inactivated influenza vaccine in adults and children with asthma. N Engl J Med. Nov 22 2001;345(21):1529-36. [Medline]. [Full Text].
Esposito S, Marchisio P, Bosis S, et al. Clinical and economic impact of influenza vaccination on healthy children aged 2-5 years. Vaccine. Jan 30 2006;24(5):629-35. [Medline].
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McClellan K, Perry CM. Oseltamivir: a review of its use in influenza. Drugs. 2001;61(2):263-83. [Medline].
Montalto NJ, Gum KD, Ashley JV. Updated treatment for influenza A and B. Am Fam Physician. Dec 1 2000;62(11):2467-76. [Medline].
Pearson ML, Bridges CB, Harper SA, et al. Influenza vaccination of health-care personnel: recommendations of the Healthcare Infection Control Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Feb 24 2006;55(RR-2):1-16. [Medline]. [Full Text].
Penn CR, Osterhaus A. Zanamivir: a rational approach to influenza B. Scand J Infect Dis. 2001;33(1):33-40. [Medline].
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Treanor JJ. Influenza virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, PA: Churchill; 2000:1824-49.
WHO. Influenza A (H1N1): Special Highlights. World Health Organization. Available at http://www.who.int/en. Accessed June 11, 2009.
influenza, flu, swine flu, swine influenza, H1N1, 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, treatment, diagnosis
Hakan Leblebicioglu, MD, Chairman, Professor, Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University Medical School, Turkey
Hakan Leblebicioglu, MD is a member of the following medical societies: American Society for Microbiology
Disclosure: Nothing to disclose.
Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society
Disclosure: Nothing to disclose.
David Jaimovich, MD, Chief Medical Officer, Joint Commission International and Joint Commission Resources
David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.
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
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching
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
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None
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