What are the recommended timing, dosage, contraindications, and special considerations (e.g., pregnancy, immunosuppression, egg allergy) for administering the yellow fever vaccine?

Yellow Fever Vaccine Administration

Administer a single 0.5 mL subcutaneous injection of reconstituted yellow fever vaccine to all persons aged ≥9 months traveling to endemic areas of Africa or South America, with the vaccine providing long-lasting immunity from a single dose in most healthy individuals. 1, 2

Dosage and Administration

Standard Dosing:

• A single subcutaneous injection of 0.5 mL of reconstituted vaccine is the standard dose for all ages ≥9 months 1, 2
• The vaccine must be reconstituted with the supplied diluent (Sodium Chloride Injection USP) and used within 60 minutes of reconstitution 1, 2
• Once reconstituted, maintain the vaccine at 35°F–46°F (2°C–8°C) and discard any unused portion after 1 hour 1
• If inadvertently administered intramuscularly rather than subcutaneously, the dose does not need to be repeated as the immune response is likely unaffected 1, 3

Timing Requirements:

• Administer the vaccine at least 10 days before travel to ensure protective immunity and meet International Certificate of Vaccination or Prophylaxis (ICVP) validity requirements 4, 2
• The ICVP becomes valid 10 days after vaccination and remains valid for 10 years under International Health Regulations 3, 4, 2

Booster Dosing Considerations

Current Evidence on Duration of Immunity:

• A single dose provides long-lasting protection in most healthy individuals, with evidence suggesting immunity persists for decades and may be lifelong 3, 5
• However, International Health Regulations still require revaccination at 10-year intervals for international travel purposes 3
• Recent meta-analysis data show pooled seroprotection rates of 94% in healthy travelers from non-endemic areas at ≥10 years post-vaccination 5

When to Consider Booster Doses:

• Individuals at continued high risk (prolonged stays in highly endemic areas like rural West Africa, laboratory personnel handling virulent virus) may receive a booster dose after 10 years 2
• Persons who may not have had adequate initial immune response (women vaccinated during pregnancy, HIV-infected persons, hematopoietic stem cell transplant recipients) and who continue to be at risk may receive an additional dose 2
• If the date of prior vaccination cannot be ascertained and vaccination is required, administer a booster dose 3

Absolute Contraindications

Do NOT administer yellow fever vaccine to:

• Infants younger than 6 months of age due to substantially elevated risk of vaccine-associated neurotropic disease (YEL-AND) 4, 2
• Persons with immunodeficiency diseases including symptomatic HIV infection 4
• Lactating women providing breastmilk to infants younger than 9 months of age (three cases of vaccine-associated neurotropic disease have been reported worldwide in exclusively breastfed infants <1 month old whose mothers were vaccinated) 2

Precautions (Relative Contraindications)

Exercise caution and carefully weigh risks versus benefits in:

• Infants aged 6-8 months (postpone travel to endemic areas if possible) 4
• Adults aged ≥60 years, particularly for first-time vaccination, due to increased risk of serious adverse events including vaccine-associated viscerotropic disease (YEL-AVD) and neurotropic disease 4, 2
• Pregnant women (vaccination should only be given if travel to high-risk endemic areas cannot be avoided; animal reproduction studies have not been conducted, and transplacental infection with vaccine virus can occur) 4, 2
• Breastfeeding women providing milk to infants ≥9 months of age (discuss risks and benefits) 2
• Patients on systemic corticosteroid therapy (may have immunosuppressive effect that decreases immunogenicity and increases adverse event risk) 2
• Persons with asymptomatic HIV infection (seroconversion rate is reduced and depends on viral load and CD4+ count; documentation of protective antibody response is recommended before travel) 2

Egg Allergy Considerations

• Anaphylaxis has been reported even in persons with no history of reactions to vaccine components 1
• All persons must be observed for at least 15 minutes following vaccination, with epinephrine 1:1,000 readily available 1
• Advise all vaccinees of delayed allergic reaction signs (urticaria, angioedema, rash, dyspnea, bronchospasm, pharyngeal edema, wheezing, throat tightness) and to seek immediate medical care if symptoms develop 1

Documentation Requirements

Critical for International Travel:

• Vaccination must be administered at an approved Yellow Fever Vaccination Center designated by state/territorial health departments 4, 2
• Travelers must receive a completed International Certificate of Vaccination or Prophylaxis (ICVP) bearing the provider's signature and the official yellow fever vaccination center stamp 4, 2
• Incomplete or inaccurate ICVP documentation can result in quarantine for up to 6 days, denied entry, or forced revaccination at the point of entry 4

Medical Waivers:

• If vaccination is medically contraindicated, complete the "Medical Contraindications to Vaccination" section of the ICVP with a signed, dated exemption letter on letterhead bearing the official vaccination center stamp 1, 4
• Warning: Destination countries may not accept medical waivers, and travelers face increased infection risk 4

Interaction with Other Vaccines

• When not administered concomitantly with other live vaccines, wait at least 4 weeks (30 days) between yellow fever vaccine and other live viral vaccines 3, 2
• If given concomitantly, administer at separate injection sites using separate syringes 2
• Do not combine or mix yellow fever vaccine with any other vaccine 2
• Chloroquine does not adversely affect antibody responses despite inhibiting vaccine replication in vitro 2
• Immune globulin (5 cc) does not alter immunologic responses to yellow fever vaccine 2

Special Safety Considerations

Blood Donation:

• Defer blood donation for 2 weeks after yellow fever vaccination due to documented transfusion-related transmission of vaccine virus 1, 3

Expired Vaccine:

• Do not use vaccine after its expiration date 1, 6
• If expired vaccine is inadvertently administered, do not count the dose as valid and repeat with non-expired vaccine following a 28-day interval 1, 6

Adverse Event Monitoring:

• Monitor elderly individuals (≥60 years) for signs and symptoms of vaccine-associated viscerotropic disease, which typically occurs within 10 days post-vaccination 2
• Reactions are typically mild (headaches, myalgia, low-grade fevers in <25% of vaccinees), but serious adverse events including YEL-AND and YEL-AVD are rare 4

Common Pitfalls to Avoid

• Failing to administer vaccine at least 10 days before travel (ICVP will not be valid upon arrival) 4, 2
• Not obtaining proper ICVP documentation with official stamp (can cause serious travel disruptions) 4
• Using reconstituted vaccine beyond 1 hour (vaccine must be discarded) 1, 2
• Vaccinating infants <9 months or immunosuppressed persons without careful risk-benefit assessment (contraindicated in most cases) 4, 2
• Not screening for pregnancy, breastfeeding status, or age ≥60 years before first-time vaccination (these are important precautions) 4, 2