Influenza Vaccine

Aka: Influenza Vaccine, Trivalent Influenza Vaccine, Quadrivalent Influenza Vaccine, Fluzone, Inactivated Influenza Vaccine, TIV Vaccine, Fluarix, FluLaval, Flublok, Flucelvax, Fluad

1. See Also
   1. Influenza
   2. Live Attenuated Influenza Vaccine (Flumist, LAIV)
2. Background: Vaccine Production
   1. Trivalent Vaccine and quadrivalent Vaccine
      1. Trivalent Vaccines cover 2 Influenza A Viruses (H1N1, H3N2) and 1 Influenza B virus
      2. Quadrivalent Vaccines cover one additional Influenza B virus (preferred Vaccine if available)
      3. Flumist is available as quadrivalent Vaccine as of 2013
      4. Fluarix, FluLaval and Fluzone are available in trivalent and quadrivalent as of 2013
      5. Other injectable Influenza Vaccines are available as trivalent Vaccines only
   2. High dose and augmented Vaccines
      1. Indicated for older patients (age >65 years old), to improve immune response to Vaccine
      2. Increased risk of injection site reactions
      3. Preparations
         1. Fluzone high dose (4 fold more Antigen than standard dose)
         2. Fluad augmented with adjuvant component
   3. H1N1 Coverage
      1. H1N1 is included in Influenza Vaccine as of 2011 in U.S.
   4. Live and inactivated Vaccines
      1. FlumistVaccine is live, attenuated Influenza Vaccine
      2. All other Vaccines (injectable) are inactivated
   5. Egg-grown Vaccine versus non-Egg grown Vaccine
      1. Egg-grown Vaccines (hens egg-grown Vaccines, requires >1 year of growth)
         1. Preparations: Fluzone, Fluarix, FluLaval
         2. Available as trivalent or quadrivalent Vaccines
         3. Avoid in egg allergy (Allergic Reaction to lightly cooked egg)
      2. Cell culture Vaccine: Flucelvax
         1. Approved only for adults
         2. May contain trace amounts of egg protein (avoid in severe egg allergy)
         3. Available as trivalent Vaccine
         4. More rapid production of flu Vaccine
      3. Recombinant Vaccine: Flublok (RIV3)
         1. Trivalent Recombinant Hemagglutinin Influenza Vaccine
         2. Approved for ages 18 to 49 years old
         3. Contains only virus protein related to Immunity with no egg protein
            1. Safe even in severe egg allergy
         4. Available as trivalent Vaccine
         5. More rapid production of flu Vaccine
   6. Virus strains chosen based on:
      1. Virulence
      2. Lack of Immunity in community
      3. Technical limitations on virus culture
   7. Vaccine developed and potency tested over 6-7 months
      1. Inject sheep and testing Antigenicity
      2. Measure effective hemagglutinin concentration
      3. Develop reference strains
3. Efficacy
   1. Onset of Immunity at approximately 2 weeks from the time of Vaccination
   2. General
      1. Prevents illness in 70% healthy people age <65 years
      2. Prevents 30-70% Pneumonia hospitalizations in elderly
   3. Populations who benefit greatest from Vaccine (highest efficacy, best outcome data)
      1. Children (see NNT below)
      2. COPD
         1. Significantly reduced rate of hospitalization, Pneumonia, serious respiratory illness
         2. Poole (2006) Cochrane Database Syst Rev (1): CD002733 [PubMed]
   4. Number Needed to Treat (NNT)
      1. Vaccine NNT is highest in Children: 8
         1. However limited data in age under 2 years (the most seriously affected population)
      2. Best years (in which Vaccine matched predominant strains) Vaccine NNT: 33
      3. Worst years (in which Vaccines poorly matched active strains) Vaccine NNT: 100
      4. References
         1. Newman in Herbert (2013) EM:Rap 13(12): 15-6
         2. Jefferson (2010) Cochrane Database Syst Rev (7): CD001269 [PubMed]
         3. Jefferson (2012) Cochrane Database Syst Rev (8):CD004879 [PubMed]
4. Indications: High risk groups (but recommended for all patients 6 months and over as of 2012)
   1. Age 65 years and older
   2. All children ages 6 months to 18 years
   3. Nursing Home and Chronic care residents
   4. Chronic pulmonary disease
      1. Asthma
      2. COPD
   5. Chronic disease (especially those requiring frequent hospitalization)
      1. Chronic Kidney Disease
      2. Chronic Liver Disease
      3. Heart disease
      4. Diabetes Mellitus
      5. Sickle Cell Anemia
   6. Long term Aspirin use under age 18 years
      1. Prevents Reye's Syndrome
   7. Vectors
      1. Health care workers
      2. Nursing Home personnel
      3. Family members of high risk patients
      4. Families and child care workers caring for children under age 5 years
   8. Essential service providers
   9. Students in Institutional settings
   10. Human Immunodeficiency Virus or other immunosuppresion
   11. Travel to tropics any time of year
   12. Travel to Southern Hemisphere April to September
   13. Pregnancy (second and third trimester)
       1. Administer injectable Influenza Vaccine in any trimester (do not use Flumist)
   14. Breast Feeding
5. Contraindications
   1. Age under 6 months
   2. Anaphylaxis or severe allergy to eggs or other Vaccine components
      1. Exception: Flublok (Recombinant Vaccine) contains no egg protein
      2. See egg allergy under protocol below
   3. Acute febrile illness
   4. History of Guillain Barre Syndrome
6. Protocol
   1. Site
      1. Adults and older children: Deltoid
      2. Infants and young children: Anterolateral thigh
   2. Timing
      1. Clinic Visits starting in September (typically recommended by end of October)
      2. Nursing Homes in October-November (not too early!)
   3. Dosing Frequency
      1. Annual Vaccination is recommended
         1. Waning Immunity even when the prior year's Vaccine constituents were identical (e.g. 2013 to 2014)
         2. Typically one or more Influenza Vaccine Antigens are different from the year prior
      2. Children (Age 6 months to 8 years)
         1. First Immunization year: 2 doses, 1 month apart before December
         2. Subsequent Immunization years: 1 dose before December
      3. Adults and children over age 9 years
         1. Dosing: 1 dose per year before December
         2. Consider a second dose if first dose given early
   4. Dose
      1. Age 6 to 35 months: 0.25 ml
      2. Age 3 years or older: 0.50 ml (contains 45 mcg hemagglutinin Antigen per dose)
      3. Age 65 years of older
         1. Standard dose as above (45 mcg hemagglutinin) or
         2. High dose Fluzone (180 mcg hemagglutinin)
            1. No evidence as of 2012 that high-dose significantly improves Immunity
            2. NNT 218 to prevent one additional case of Influenza in age over 65 years
            3. High dose Vaccine is associated with more local reactions and flu-like symptoms
   5. Egg Allergy precautions
      1. Observe for at least 30 minutes for reaction after Influenza dose
      2. Patient tolerates scrambled egg without reaction
         1. Standard Vaccine may be used
      3. Hives after egg exposure
         1. Trivalent Recombinant Influenza Vaccine (Flublok, RIV3) if age 18-49 years or
         2. Standard Inactivated Influenza Vaccine
      4. Systemic reaction to egg exposure (Anaphylaxis)
         1. Trivalent Recombinant Influenza Vaccine (Flublok, RIV3) if age 18-49 years
         2. Administer standard Inactivated Influenza Vaccine ONLY if prepared to treat for Anaphylaxis
      5. References
         1. Grohskopf (2014) MMWR Morb Mortal Wkly Rep 63(32): 691-7 [PubMed]
   6. Other Vaccinations on same day
      1. Influenza Vaccine may be given on the same day as others (e.g. Shingles Vaccine, penumococcal Vaccine)
      2. Use a different extremity for each Vaccine or choose entry sites at least 1 inch apart
      3. If Shingrix (Shingles Vaccine that contains adjuvant) given, avoid Fluad (contains adjuvant) on same day
7. Preparations
   1. Standard preparations (available as trivalent and the preferred, quadrivalent)
      1. Fluzone IM (standard preparation)
      2. Fluzone Intradermal
         1. Introduced in 2012, as potentially a less uncomfortable injection
         2. Similar efficacy to the intramuscular Fluzone
         3. Associated with more local skin reactions than the Intramuscular Injection
   2. High dose and augmented Vaccines (age over 65 years old)
      1. High risk of injection site reactions
      2. Fluzone high dose
      3. Fluad (augmented with adjuvant component)
   3. Other Vaccines
      1. Intranasal Influenza Vaccine (Flumist)
         1. Offered in 2019 for ages 2-49 years old, non-pregnant, who refuse injectable Influenza Vaccine
         2. Was not recommended in 2016 due to questionable efficacy, but considered equivalent in 2019
8. Adverse Effects
   1. No longer contains thimerosal
   2. Gastrointestinal adverse effects
   3. Febrile Seizure
   4. Low Grade Fever (<101)
      1. Occurs in 12% of children aged 1-5 years old
   5. Oculorespiratory Syndrome
      1. Conjunctival injection, cough, Wheezing and difficult swallowing
      2. Develops 2-3 after Influenza Vaccine, and resolves within 24 hours
   6. No longer significantly associated with Guillain-Barre
      1. Swine Influenza vacine (1976) was associated with increased risk (RR 4-8)
      2. Gullain-Barre occur in up to 1 per million doses (but likely much higher risk with Influenza infection)
      3. Kwong (2013) Lancet Infect Dis 13(9): 769-76 [PubMed]
   7. Influenza Vaccine is safe in infants and children
      1. France (2004) Arch Pediatr Adolesc Med 158:1031-6 [PubMed]
9. Resources
   1. CDC Immunization Schedules (last accessed 10/28/2020)
      1. https://www.cdc.gov/vaccines/schedules/
10. References
    1. (2016) Presc Lett 23(10)
    2. (2015) Presc Lett 22(9):49-50
    3. (2014) Presc Lett 21(9): 50
    4. (2013) Presc Lett 20(10): 55
    5. (1999) Preparing for the Next Pandemic telecast, CDC
    6. (1997) Am Fam Physician 56(1):279-282 [PubMed]
    7. Ackerman (2015) Am Fam Physician 92(6): 460-8 [PubMed]