Influenza - A Primer

Information below is adapted primarily from information provided by the Centers for Disease Control (CDC) but also from other authoritative organizations including the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), and The American Academy of Pediatrics (AAP). Some guidance is adapted from local circumstances.

Regardless of the source no guideline can fit every clinical circumstance. It is crucial that clinicians exercise informed clinical judgment in the approach to persons ill with suspected or diagnosed influenza.

  • Epidemiology
  • Illness/Diagnosis
  • Treatment/Prophylaxis
  • Vaccine
  • Infection Prevention

Epidemiology of Influenza

In the United States, annual epidemics of influenza occur typically during the late fall through early spring. Influenza viruses can cause disease among persons in any age group, but rates of infection are highest among children. During these annual epidemics, rates of serious illness and death are highest among persons aged ≥65 years, children aged <2 years, and persons of any age who have medical conditions that place them at increased risk for complications from influenza. Influenza epidemics were associated with estimated annual averages of approximately 36,000 deaths during 1990--1999 and approximately 226,000 hospitalizations during 1979--2001.

In April 2009, a novel influenza A (H1N1) virus, 2009 influenza A (H1N1), that is similar to but genetically and antigenically distinct from influenza A (H1N1) viruses previously identified in swine, was determined to be the cause of respiratory illnesses that spread across North America and was identified in many areas of the world by May 2009. Influenza morbidity caused by 2009 pandemic influenza A (H1N1) remained above seasonal baselines throughout spring and summer 2009 and was the cause of the first pandemic since 1968. In the United States, the pandemic was characterized by a substantial increase in influenza activity that was well beyond historical norms in September 2009, peaking in late October 2009, and returning to seasonal baseline by January 2010

In typical flu seasons approximately 60% of hospitalizations and 90% of influenza related deaths occur in persons greater than 65 years of age. Illness due to 2009 H1N1 Influenza A differed notably from that of typical seasonal influenza A in that severe illness occurred more commonly in younger age groups.The graphic below illustrates the differing epidemiology of illness due to recent influenza A strains.

Influenza Epidemiology

Cumulative rate of hospitalizations during three influenza seasons, by age group ---
Emerging Infections Program, United States, 2007--2010

Influenza caused by 2009 pandemic influenza A (H1N1) virus is expected to continue to occur during future winter influenza seasons in the Northern and Southern Hemispheres, but whether 2009 pandemic influenza A (H1N1) viruses will replace or co-circulate with one or more of the two seasonal influenza A virus subtypes (seasonal H1N1 and H3N2) that have co-circulated since 1977 is unknown.

Clinical Illness Due to Influenza

  • The typical incubation period for influenza is 14 days (average: 2 days). Infected persons may be infectious to others even before they are clinically ill (see influenza transmission).
  • Typical influenza signs and symptoms are fever, cough, sore throat, myalgias, headache, and prostration.
  • CDC case definition - Fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat in the  absence of a known cause other than influenza.
  • Fever is not invariably present; multiple other signs and symptom may be.
  • Complications have included post-influenza bacterial pneumonias - Streptococcus pneumoniae, Staphylococcus aureus (including MRSA).
  • Severe illness and death tends to occur among those with traditional risk factors. According to the American Academy of Pediatrics certain children were at particular risk of complications in the 2009-2010 pandemic flu season.
  • Severe influenza viral pneumonia in young healthy individuals occurred in the 2009-2010 pandemic flu season.

How is Influenza diagnosed?

  • Point of care nasopharyngeal swab rapid tests have only a 10-70% sensitivity for detecting infection with influenza.
    • Rapid tests can distinguish influenza A from influenza B.
    • A negative rapid test does not rule out influenza.
  • Influenza PCR available at reference laboratories (and some hosptital labs)
    • Definitive but not always timely
    • Expensive; usually performed only on those sick enough to require hospitalization
  • Click here for a table listing all influenza diagnostic methods
  • Outpatient diagnosis will depend upon clinical likelihood and current epidemiology.

Who Should be Treated for Influenza?

  • Treatment is recommended for all hospitalized patients with confirmed, probable or suspected influenza.
  • Early empiric treatment should be considered for outpatients ill with influenza like illness who are at higher risk for influenza-related complications if treatment can be initiated within the first 48 hrs.
  • Signs and symptoms of severe illness due to suspected influenza (respiratory distress, confusion, severe dehydration) are an indication for immediate treatment, regardless of previous health or age. Infants and young children may manifest severe disease in a variety of ways.
  • Because of limitations of diagnostic tests treatment decisions usually will have to be made empirically.

For the 2016-2017 flu season treatment/prophylaxis with oseltamivir (or zanamavir) is recommended. Click here for treatment/prophylaxis regimens in general.

When should prophylaxis be considered for persons exposed to persons ill with confirmed of likely influenza?

  • Consider for:
    • Persons who are at higher risk for complications of influenza and are a close contact of a person with confirmed, probable, or suspected influenza during that person’s infectious period.
    • Health care personnel, public health workers, or first responders who have had a recognized, unprotected close contact exposure to a person with confirmed, probable, or suspected influenza during that person’s infectious period if they are at higher risk of complications of influenza.
  • Antiviral agents should not be used for post exposure chemoprophylaxis in healthy children or adults based on potential exposures in the community, school, camp or other settings. Chemoprophylaxis generally is not recommended if more than 48 hours have elapsed since the last contact with an infectious person.
  • Early treatment is an emphasized alternative to chemoprophylaxis after a suspected exposure. Household or close contacts (with risk factors for influenza complications) of confirmed or suspected cases can be counseled about the early signs and symptoms of influenza, and advised to immediately contact their health care provider for evaluation and possible early treatment if clinical signs or symptoms of influenza develop.

How might treatment/prophylaxis recommendations be different depending upon the strain of circulating influenza?

  • Cases of influenza may be secondary to H1N1, H3N2, or influenza B viruses. These various strains of influenza may vary in antiviral susceptibility such that effective therapy may require different choices of antiviral agents.
  • Knowledge of what strains of influenza are circulating will depend upon information provided by public health authorities.
  • Click here for a table describing antiviral susceptibility patterns depending upon what strains of influenza are circulating.

 

Vaccination is the preferred method of preventing all strains of influenza.

Vaccination for Influenza

  • Trivalent or quadrivalent vaccines - effective against anticipated H1N1 and H3N2 influenza A  strains as well as one strain of influenza B (two strains of influenza B in the case of quadrivalent vaccine)
  • Indicated for all persons aged 6 months of age or greater (click here for prioritization in event of vaccine shortage)
  • Children aged 6 months to 8 years may need two doses of vaccine.
  • Available as either Trivalent/Quadrivalent Inactivated Influenza Vaccine or Live Attenuated Influenza Vaccine (LAIV). LAIV was determined to be ineffective in the 2015-16 season so is not recommended for the 2016-2017 flu season. Previousy, LAIV was indicated for healthy, nonpregnant persons aged 6 mo - 49 years (see contraindications below).
  • A "high dose" vaccine (trivalent) is available for immunization of persons aged 65 years or greater.
  • Quadrivalent vaccine is now also available in a form for intradermal adminstration.
  • A recombinant (not cell culture based) trivalent vaccine is available for those with serious egg allergy.
  • To see a summary table of this somewhat bewildering choice of vaccine click here. This table describes vaccine characteristics and indications.
  • Safe and effective in preventing influenza illness/complications
  • In addition to preventing clinical illness in individuals vaccination can also provide these benefits:
    • Decreased transmission of infection
    • Decreased employee illness and absenteeism
    • Decreased demands on limited quantities of antiviral medications

Vaccine Adverse Reactions/Contraindications (CDC Summary Table)

  • Injectable inactivated influenza vaccine
    • Adverse Reactions
      • Local reactions - 15%-20%
      • Fever, malaise - not common
      • Allergic reactions - rare
      • Neurological - very rare reactions
    • Contraindication - severe egg allergy; previous Guillain Barre Syndrome within 6 weeks of previous influenza vaccine and moderate or severe acute illness are relative contraindications.
  • Live Attenuated Influenza Vaccine (LAIV) - Not recommended for 2016-17!
    • Contraindications
      • Children younger than 2 years of age
      • Persons 50 years of age or older
      • Persons with chronic medical conditions
      • Children and adolescents receiving long-term aspirin therapy
      • Immunosuppression from any cause
      • Pregnant women
      • Severe (anaphylactic) allergy to egg or other vaccine components
      • History of Guillain-Barré syndrome within 6 weeks of previous influenza vaccine is a relative contraindication.
      • Children younger than 5 years with recurrent wheezing
      • Moderate or severe acute illness is a relative contraindication.
  • Live Attenuated Influenza Vaccine - Adverse Reactions
    • Children
      • no significant increase in URI symptoms, fever, or other systemic symptoms
      • significantly increased risk of asthma or reactive airways disease in children 12-59 months of age
    • Adults
      • significantly increased rate of cough, runny nose, nasal congestion, sore throat, and chills reported among vaccine recipients
      • no increase in the occurrence of fever
    • No serious adverse reactions identified

Healthcare Workers and Live Attenuated Influenza Vaccine (LAIV) - Not recommended for 2016-17!

  • Unless healthcare workers are caring for patients on hematopoietic stem cell transplant units where patients are in specialized "reverse" isolation they can receive LAIV without the need for special precautions.
  • LAIV transmission from a recently vaccinated person causing clinically important illness in an immunocompromised contact has not been reported.

Simultaneous Administration of LAIV and Other Vaccines

  • Inactivated vaccines can be administered either simultaneously or at any time before or after LAIV.
  • Other live vaccines can be administered on the same day as LAIV.
  • Live vaccines not administered on the same day should be administered at least 4 weeks apart.

Influenza Vaccine - Frequently Asked Questions

Infection Prevention - General

  • Hand hygiene and respiratory etiquette
    • Signage with instructions prominently displayed
    • Hygiene/respiratory etiquette “stations”
  • Segregation of patients with influenza like illness (ILI) in waiting rooms, ERs, urgent cares
  • Surgical masks for patients suffering with ILI and healthcare workers evaluating them

Influenza Infection Prevention - Hospital

  • All hospitalized patients with influenza like illness should be placed in droplet isolation. Any healthcare workers (HCWs) entering the room should follow standard precautions, wear a surgical mask, and use eye protection if anticipating contact within 6 feet of the patient.
  • HCWs should use N95 respirators if involved in procedures likely to cause aerosolization – intubation, bronchoscopy, open airway suctioning, autopsy

Hospital Isolation for Influenza

  • Isolation for confirmed or suspected influenza should be maintained for seven days from symptom onset or until symptoms abate whichever is longer.
  • Isolation can be discontinued if a rapid test for influenza is negative and influenza is judged unlikely by the responsible physician.
  • It is not necessary to have a negative laboratory result for influenza prior to discontinuing isolation if a physician judges infection unlikely.

Healthcare Worker Illness

  • Healthcare workers with suspected or confirmed influenza should be excluded from work for at least 24 hours after they no longer have a fever without the use of fever-reducing medicines – avoid “presenteeism.”
  • Healthcare workers returning to work after influenza like illness who work in areas where severely immunocompromised patients are provided care should be considered for temporary reassignment or exclusion from work for 7 days from symptom onset or until the resolution of symptoms, whichever is longer.