Influenza (Flu)

 

Pathophysiology:

 

Influenza is a contagious, acute respiratory illness that affects both the upper and lower respiratory tracts. The influenza viruses (A, B and C) are members of the Orthomyxoviridae family of RNA viruses, and influenza type A and B are two the major human pathogens.

 

Influenza A is known to cause the most severe outbreaks due to the ability of the hemagglutinin and neuraminidase antigens on its surface to undergo frequent and extensive antigenic variation; an alteration of those surface antigens that allows the virus to more easily evade the host’s immune response.

 

Since the hemagglutinin and neuraminidase of influenza B undergo antigenic variation less frequently, outbreaks tend to be milder and cause less severe disease.

 

Influenza C virus is associated with minor illness in humans, ranging from asymptomatic infection to common cold-like symptoms. 

 

Influenza virus is acquired via aerosolized respiratory secretions of acutely infected individuals. Common forms of transmission include coughing, sneezing and hand-to-hand contact, and less often via fomite transmission. After the 18-72 hour incubation period, the virus begins to replicate within the infected ciliated columnar epithelial cells of the respiratory tract, and eventually leads to necrosis and desquamation of those cells.

 

This results in loss of the ciliary-mucous elevator and the inability to properly clear secretions.  The period of contagiousness ranges from 1 day before symptoms become apparent to 5-7 days after symptom onset for adults and up to 10 days after symptom onset for children.

 

Epidemiology:

 

  • Influenza outbreaks have a seasonal distribution, occurring worldwide almost exclusively during the winter months

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  • 2-3 different influenza strains circulate concurrently
  • School-aged children have the highest attack rate during a community outbreak and serve as a major source of transmission
  • Average of 200,000 hospitalizations per year

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  • Death rate: 0.5-1 per 1,000 cases
  • Majority of deaths in individuals over 65 years of age

 

Clinical Manifestations:

 

Classically you see the abrupt onset of fever, headache, myalgias, and malaise, along with typical symptoms of an upper respiratory tract infection such as cough, sore throat and rhinitis. Additionally, children may experience anorexia, nausea, vomiting and diarrhea. Over 50% of infected children will have a temperature to greater than 39 oC (102.2 oF)

 

Diagnosis:

 

  • Gold Standard: Throat, nasopharyngeal, or sputum viral culture
  • Test Time:      3-10 days
  • Rapid Influenza diagnostic test: Detects influenza antigens in nasopharyngeal, throat or sputum sample
  • Test Time:     Less than 30 min
  • Sensitivity:    50-70%; less than viral culture and RT-PCR
  • Direct Fluorescent Antibody Test: Detects influenza A or B in nasal secretion samples
  • Test Time:    1-4 hours
  • Real-time polymerase chain reaction test: PCR detection of viral genome in nasal secretion samples
  • Test Time:    1-6 hours
  • Serologic Testing: Influenza A or B antibody titers during both acute and convalescent phase required to confirm infection
  • Test Time:    > 10 days

 

  • All specimens should be collected within 4-5 days of symptom onset
    • Should consider sending viral cultures to confirm all rapid test results, especially when community prevalence is low

 

Treatment:

 

  • Symptomatic relief:
    • Fluids and rest
    • Acetaminophen or NSAIDs: Fever, headache, and myalgias
    • Avoid salicylates in individuals less than 18 years of age due to risk of Reye’s Syndrome
            
  • Hospitalized patients placed on droplet and contact precaution
                          
  • Neuraminidase Inhibitors: Active against both influenza A and B with reduction of symptoms by 1-2 days.  All persons with suspected or confirmed influenza requiring hospitalization should receive antiviral treatment unless there is a contraindication.
    • Zanamivir (Relenza) : Inhaled preparation approved for use in individuals 7 years of age and older that present less than 48 hours after symptom onset
         
      • Influenza prophylaxis in individuals 5 years of age and older
      • Side Effects / Warnings - Bronchospasm has been known to occur after use, so consider use carefully and have a bronchodilator available in those individuals with underlying airway disease.
                
    • Oseltamivir (Tamiflu) : Oral preparation approved for use in individuals 1 year of age and older that present less than 48 hours after symptom onset
      • Influenza prophylaxis in individuals 1 year of age and older
      • Side Effects / Warnings - Neuropsychiatric side effects have been reported in children (hallucinations, confusion, delirum, self-harm) so counsel parents and monitor appropriately.
      • The US Food and Drug Administration (FDA)  expanded the approved use of oseltamivir (Tamiflu, Genentech) to treat children as young as 2 weeks old who have shown symptoms of influenza for no longer than 2 days.

 

Complications:

 

  • High Risk of Complications
     
    • Individuals greater than 65 years of age
    • Children less than 5 years of age
    • Pregnant women
    • Individuals with chronic conditions such as asthma, diabetes mellitus, heart disease, and chronic lung disease

 

Complications seen:

  • Otitis Media
  • Pneumonia:
    • Bacterial: Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus
    • Primary influenza viral pneumonia: Uncommon but high fatality rate
  • Reye Syndrome: Primarily associated with influenza B and exclusively seen in children taking aspirin
  • Myositis
  • Myocarditis
  • Neurologic:
     
    • Febrile seizures
    • Aseptic meningitis
    • Acute cerebellar ataxia
    • Postinfectious encephalitis

 

Prevention:

  • Annual Trivalent seasonal influenza vaccine: Yearly preparation that contains 2 strains of influenza A and 1 strain of influenza B anticipated to circulate during that season
     
    • Vaccine should be offered as soon as available each season
      • Ideal time October-December each year
                           
    • Injectable trivalent inactivated influenza vaccine:
       
      • Contains inactivated subvirion or surface antigen
      • Route: Intramuscular (IM) or intradermal (ID)
      • IM recommended for children 6 months of age and older
      • ID recommended for 18-64 year olds
      • Contraindications:
        • Infants under 6 months
        • Severe allergic reaction to vaccine component following prior dose
        • Moderate to severe acute illness
        • History of Guillain-Barre’ Syndrome within 6 weeks of a previous influenza vaccine dose
                                 
    • Intranasally administered live-attenuated influenza vaccine
             
      • Contains live, attenuated virus
      • Route: Intranasal spray
      • Approved for healthy individuals ages 2-49 years
      • Contraindications:
                      
        • Children who have received another live-virus vaccine within the last 4 weeks
        • Children under 5 with recurrent wheezing
        • Chronic conditions:
           
          • Metabolic disease
          • Diabetes mellitus
          • Asthma
          • Hemoglobinopathy
          • Chronic cardiopulmonary disorder
          • Renal dysfunction
        • Immunocompromised or on immunosuppressive therapy
        • Children on salicylates
        • Pregnant women
        • Severe allergic reaction to vaccine component following prior dose
        • Moderate to severe acute illness
        • History of Guillain-Barre’ Syndrome within 6 weeks of a previous influenza vaccine dose
        • Although not a contraindication, individuals receiving the live vaccine should avoid close contact with immunocompromised individuals for at least 7 days

 

Minor illnesses, with or without fever, mild URI symptoms and allergic rhinitis are not contraindications to vaccination

 

  • Children 6 months – 8 years of age receiving vaccine for the first time need a second dose administered at least 4 weeks after the first dose

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  • Children 9 years or older only require one dose yearly

 

The CDC provides a useful and up to date website with information for patients and providers alike on influenza.  Click on the logo below to go to their site.

 

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References:

  1. Dolin R. Chapter 187. Influenza. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=9094339
  2. Centers for Disease Control and Prevention. Influenza: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book. 2012; 12. http://www.cdc.gov/vaccines/pubs/pinkbook/flu.html
  3. Edwards M. Clinical features and diagnosis of seasonal influenza in children. Up-to-date. http://www.uptodate.com/contents/clinical-features-and-diagnosis-of-seas...
  4. Seasonal Influenza (flu): Key facts about influenza (flu) & flu vaccine. Centers for Disease Control and Prevention. http://www.cdc.gov/flu/keyfacts.htm
  5. Seasonal Influenza (Flu): Rapid Diagnostic Testing for Influenza. Centers for Disease Control and Prevention. http://www.cdc.gov/flu/professionals/diagnosis/rapidclin.htm
  6. Committee on Infectious Disease. Recommendations for Prevention and Control of Influenza in Children, 2012-2013. Pediatrics. 2012; 120 (4): 780-792. http://pediatrics.aappublications.org/content/130/4/780.full.pdf+html