What are the current recommendations for influenza vaccination in children, including age eligibility, dosing schedule, and the advantages and disadvantages of trivalent versus quadrivalent (tetravalent) influenza vaccines?

Influenza Vaccination in Children: Recommendations and Vaccine Formulation Comparison

Primary Recommendation

Annual influenza vaccination is recommended for all children 6 months of age and older, with quadrivalent inactivated influenza vaccine (IIV4) preferred over trivalent formulations when available, as it provides broader protection against both influenza B lineages without compromising safety or efficacy. 1

Age Eligibility and Dosing Schedule

Minimum Age

• Influenza vaccination begins at 6 months of age for all children 1
• Live attenuated influenza vaccine (LAIV) is only approved for children ≥2 years of age 1, 2

Dose Volume by Age

• 6-35 months: May receive either 0.25 mL or 0.5 mL depending on the specific vaccine product 1, 3
• ≥36 months (3 years) and older: Receive standard 0.5 mL dose, identical to adult dosing 1, 4

Number of Doses Required

• First-time recipients <9 years old: Require 2 doses separated by at least 4 weeks to achieve adequate immune response, as these children lack prior priming from natural infection or vaccination 1, 5, 2
• Previously vaccinated children (≥2 doses lifetime): Require only 1 dose per season 1, 4
• Children ≥9 years: Require only 1 dose per season regardless of vaccination history 1

Route of Administration

• Intramuscular injection in the deltoid muscle (preferred for children ≥3 years) or anterolateral thigh (acceptable for younger children) 1, 4

Trivalent vs Quadrivalent Vaccines: Advantages and Disadvantages

Quadrivalent Vaccine (QIV) - PREFERRED

Advantages:

• Broader protection: Contains 4 strains (2 influenza A + 2 influenza B lineages: Victoria and Yamagata) versus 3 strains in trivalent vaccines 1
• Addresses B lineage mismatch: Eliminates the risk of selecting the wrong B lineage, which has historically occurred in 50% of seasons when B viruses circulate 6
• Superior immunogenicity for alternate B strain: Induces robust immune responses to both B lineages, providing protection regardless of which B lineage predominates 6
• Comparable safety profile: Adverse event rates are similar to trivalent vaccines for shared strains 3, 6
• Cost-effective strategy: Despite higher vaccine cost, reduces overall healthcare burden by preventing more influenza B cases 6
• Widely available: Multiple QIV formulations are now licensed for children ≥6 months, including Fluarix Quadrivalent, FluLaval Quadrivalent, Fluzone Quadrivalent, and Flucelvax Quadrivalent 1

Disadvantages:

• Minimal disadvantages exist; the primary consideration is slightly higher vaccine acquisition cost, though this is offset by improved clinical outcomes 6

Trivalent Vaccine (TIV)

Advantages:

• Lower acquisition cost per dose 6
• Acceptable alternative when quadrivalent vaccines are unavailable 1

Disadvantages:

• Limited B lineage coverage: Contains only 1 influenza B strain, creating risk of lineage mismatch with circulating strains 1, 6
• Reduced protection: In seasons when the non-included B lineage predominates, provides no protection against that lineage 6
• Less optimal choice: The American Academy of Pediatrics recommends IIV (trivalent or quadrivalent) but does not express preference for trivalent when quadrivalent is available 1

Available Vaccine Products for Children

Inactivated Influenza Vaccines (IIV) - Ages ≥6 months

• Fluarix Quadrivalent (GlaxoSmithKline): 0.5 mL dose, thimerosal-free prefilled syringe 1
• FluLaval Quadrivalent (GlaxoSmithKline): 0.5 mL dose, thimerosal-free prefilled syringe 1
• Fluzone Quadrivalent (Sanofi Pasteur): Available in 0.25 mL (6-35 months) and 0.5 mL (≥36 months) doses 1, 3
• Flucelvax Quadrivalent (Seqirus): Cell culture-based vaccine, licensed for ≥6 months as of October 2021, demonstrated 54.6% efficacy (95% CI: 45.7%-62.1%) in children 2-18 years 1

Live Attenuated Influenza Vaccine (LAIV) - Ages ≥2 years

• FluMist Quadrivalent: Intranasal spray, only for healthy children without chronic medical conditions 1
• Important caveat: The AAP recommends IIV as the primary choice over LAIV due to inferior effectiveness of LAIV against influenza A(H1N1) in past seasons 1
• LAIV may be used only when a child would otherwise not receive any influenza vaccine (e.g., needle phobia) 1

Safety Profile

Common Adverse Reactions - IIV

Injection site reactions (most common): 1, 3

• Pain/tenderness: 47-59% after first dose
• Erythema: 27-29%
• Swelling: 15-20%

Systemic reactions: 1, 3

• Irritability: 31-43%
• Drowsiness: 26%
• Appetite loss: 19-23%
• Fever (≥100.4°F): 10-12%
• Headache, malaise, myalgia in older children: 12-28%

Important Safety Considerations

• IIV can be administered concomitantly with other vaccines, including COVID-19 vaccines, without safety concerns 1
• Egg allergy is NOT a contraindication: All children with egg allergy of any severity can receive influenza vaccine without additional precautions beyond standard vaccine administration protocols 1
• Guillain-Barré Syndrome risk is extremely low (at most 1-2 cases per 1 million vaccinees) 2

Common Pitfalls and How to Avoid Them

1. Failing to administer 2 doses to first-time recipients <9 years: These children require priming and boosting for adequate protection; a single dose provides suboptimal immunity 1, 5, 2

2. Delaying vaccination until peak influenza season: Vaccination should begin as soon as vaccine becomes available in early fall, as immune response takes 2-4 weeks to develop 2

3. Withholding vaccine due to egg allergy: This outdated practice denies protection to allergic children who can safely receive influenza vaccine 1

4. Using LAIV as first-line therapy: Given inferior effectiveness against H1N1, IIV should be the primary choice; reserve LAIV only for children who refuse injectable vaccine 1

5. Confusing dose volumes: Children 6-35 months may receive 0.25 mL or 0.5 mL depending on product; children ≥36 months always receive 0.5 mL 1, 3

6. Assuming trivalent and quadrivalent vaccines are equivalent: Quadrivalent vaccines provide objectively superior protection against influenza B and should be preferentially selected when available 6