Yellow Fever Vaccine

Yellow fever vaccination is indicated for travelers aged 9 months and older visiting areas where yellow fever transmission occurs or where entry requirements mandate proof of vaccination. Specifically, vaccination is recommended for individuals traveling to:

• Sub-Saharan Africa and endemic regions,

• South America and Central America,

• Areas designated by the World Health Organization with evidence of persistent or periodic yellow fever virus transmission,

• Countries requiring evidence of vaccination as a condition of entry.

Vaccination may be considered for infants aged 6 to 9 months if travel to high-risk endemic areas is unavoidable and the risk of yellow fever infection is substantial. Healthcare workers and laboratory personnel with potential exposure to yellow fever virus may also require vaccination based on occupational risk assessment.

Absolute contraindications preclude vaccination in the following circumstances:

• Age under 6 months: Significantly elevated risk of vaccine-associated encephalitis (YEL-AND), with historical data demonstrating 13 of 15 reported encephalitis cases occurring in infants under four months of age.

• Hypersensitivity to vaccine components: Severe allergic reaction or anaphylaxis to eggs, chicken protein, gelatin, or any other vaccine ingredient.

• Thymus disorder or history of thymectomy: Includes thymoma, myasthenia gravis, DiGeorge syndrome, and any surgical removal of the thymus gland for any reason. Risk of vaccine-associated viscerotropic disease (YEL-AVD) is approximately 6 times higher in this population.

• Symptomatic HIV infection or severe immunosuppression: CD4+ count <200 cells/mm³ or <15% of total lymphocytes in children younger than 6 years.

• Active malignant neoplasm: Particularly hematologic malignancies such as leukaemia and lymphoma.

• Organ transplantation: Current or recent (<6 months) immunosuppressive therapy following solid organ transplant.

• Primary immunodeficiencies: Severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and other cellular immune deficiencies.

Yellow fever vaccine demonstrates exceptionally high immunogenicity and durable protective efficacy.

Short-term Protection (≤3 months): Seroconversion rates (development of protective antibodies) approach 100% in healthy vaccinees across all ages, with seroprotection rates of 95–100% documented in prospective studies. In immunocompromised individuals, seroprotection rates remain high at approximately 92%.

Proper vaccine storage is critical for maintaining potency and efficacy.

• Unopened vaccine (lyophilized powder):

• Temperature: 2°C to 8°C (35°F to 46°F); aim for 5°C (41°F)

• Protection from light: Keep in original packaging

• Duration: Until expiration date on vial

• Freezing: Must not be frozen

Active Ingredient:

Yellow fever virus 17D-204 strain (live, attenuated) – minimum 1000 international units (IU) per 0.5 mL dose (equivalent to ≥4.74 log₁₀ plaque-forming units)

Produced in specified pathogen-free (SPF) chicken embryos, free of avian leukosis virus

Non-medicinal Ingredients (Excipients):

Sorbitol (stabilizer)

Gelatin (stabilizer)

Sodium chloride

L-Histidine hydrochloride

L-Alanine

Potassium chloride

Disodium phosphate dihydrate

Potassium dihydrogen phosphate

Calcium chloride

Magnesium sulfate

Lactose (in some formulations)

Water for injection

Notable absence:

No preservatives (sodium thimerosal or other antimicrobial agents) are added

Physical form:

Lyophilized (freeze-dried) powder supplied in hermetically sealed vials under nitrogen atmosphere

Reconstituted vaccine: slight pink-brown suspension

Yellow fever vaccine may be administered concurrently with the following vaccines at separate injection sites:

Measles, mumps, rubella (MMR) and other measles-containing vaccines

Polio (oral polio vaccine [OPV] and inactivated polio vaccine [IPV])

Diphtheria, tetanus, pertussis (DTP, Tdap)

Hepatitis A and B vaccines

Oral cholera vaccine

Typhoid vaccine (both oral and parenteral forms)

When administered concurrently with other live vaccines, separate injection sites and separate syringes must be used. If not given simultaneously, a minimum interval of 4 weeks is recommended between yellow fever vaccine and other live attenuated vaccines (measles, mumps, rubella, varicella, rotavirus, BCG).

Recommendation: Yellow fever vaccine should be avoided during pregnancy unless travel to a high-risk yellow fever-endemic area is unavoidable and cannot be postponed, and a high level of protection against mosquito bite exposure is not feasible.

Rationale: Wild yellow fever virus can cause severe infection in pregnancy and has been associated with fetal transmission and poor outcomes. However, the live attenuated vaccine virus carries theoretical risk, particularly in the first trimester. Limited data from surveillance of several hundred women who inadvertently received yellow fever vaccine during pregnancy have not demonstrated significant adverse fetal outcomes, suggesting that inadvertent vaccination during pregnancy is not an indication for pregnancy termination. ​

Special considerations:

Seroconversion rates (antibody response) following vaccination are lower in pregnant women compared to non-pregnant individuals; post-immunization serology (blood test to confirm immunity) may be considered ​

Individual risk assessment must carefully weigh the risk of yellow fever infection (which carries substantial maternal and fetal morbidity and mortality) against theoretical vaccine risks

If vaccination is deemed necessary, it should ideally be administered in the second or third trimester, though the vaccine can be given at any stage if infection risk is high ​

Healthcare providers should document the indication for vaccination and counsel women regarding theoretical risks

Women of childbearing potential should be counseled to avoid pregnancy for 2 months following yellow fever vaccination, though data do not support this as a strict requirement

Recommendation: Yellow fever vaccination should generally be avoided in women who are actively breastfeeding, particularly those breastfeeding infants under 9 months of age.

Rationale: Three documented cases of vaccine-strain yellow fever virus transmission through breast milk have been reported, resulting in meningoencephalitis in exclusively breastfed infants whose mothers received yellow fever vaccine during their infants' first month of life. Although the exact mode of transmission has not been definitively established, the risk of vaccination during breastfeeding is considered a precaution rather than an absolute contraindication.

Age 6 months to 9 months:

Vaccination is contraindicated in routine circumstances due to increased risk of vaccine-associated encephalitis (YEL-AND). During the pre-restriction era (1950s), 15 encephalitis cases were reported in infants, with 13 (87%) occurring in infants under 4 months and all cases occurring in infants under 7 months. The risk of YEL-AND is inversely proportional to age in this age group. ​

Vaccination may be considered only when travel to yellow fever-endemic areas is unavoidable and the risk of wild-type yellow fever infection is very high (such as during confirmed epidemics or outbreaks). Expert consultation is mandatory, and a thorough individual risk-benefit assessment must be documented.

Age 9 months to 2 years:

Vaccination is recommended for infants and young children traveling to yellow fever-endemic areas. However, immunogenicity studies demonstrate lower seroprotection rates in children vaccinated before age 2 years:

Seroprotection rate within 5 years post-vaccination: approximately 52% in children vaccinated before age 2 years

This is substantially lower than the >90% seroprotection rate in children vaccinated at age ≥2 years

Booster vaccination in early childhood: Children vaccinated before age 2 years are recommended to receive a reinforcing (booster) dose once they reach age 2 years or older, depending on planned travel to yellow fever-endemic areas. This recommendation is based on evidence of waning seroprotection 3 months to 5 years following primary vaccination in infants. Recent breakthrough infection data suggest this approach may enhance long-term protection. ​

Age ≥9 years to adolescence:

Children in this age group have immunogenicity and safety profiles similar to adults. Standard vaccination schedules and recommendations apply. A single dose provides sustained protective immunity.

General pediatric considerations:

The vaccine is well-tolerated in children

Mild systemic adverse events (fever, headache, myalgia) are reported in 20–40% of younger vaccinees, with rates typically lower in older children than infants

Serious adverse events are rare in children, with the exception of increased risk in the 6–9 months age group

Vaccination in children can be given concurrently with routine immunizations at separate injection sites

Travel-related mosquito bite prevention is essential for all children, especially those too young for vaccination or in the precautionary age groups

Recommendation: Yellow fever vaccination for individuals aged 60 years and older requires individualized risk-benefit assessment. Vaccination should only be administered when there is a significant and unavoidable risk of acquiring yellow fever infection based on travel itinerary and duration in endemic areas.

No specific cases of overdose with yellow fever vaccine have been documented in the medical literature. The vaccine is supplied as a single-dose vial containing 0.5 mL (one dose), and multi-dose vials are used in limited circumstances under strict medical supervision.

Precautions Beyond contraindications and relative contraindications previously discussed, the following precautions and special considerations apply:

Latex allergy: The rubber stopper of the vaccine vial may contain natural latex rubber. Individuals with known latex allergy should inform the healthcare provider; an alternative approach (such as using a non-latex needle or requesting pre-filled syringes) may be necessary.

Egg allergy assessment: Individuals with a history of egg allergy may safely receive yellow fever vaccine if the allergy is non-anaphylactic. For those with anaphylactic egg allergy, a skin test using a 1:10 vaccine dilution (scratch, prick, or puncture method) should be performed; if the test is negative, the vaccine may be given. If the test is positive or the history is strongly suggestive of anaphylaxis, desensitization should be performed before administering a full dose. ​

Post-vaccination blood donation: Blood donors should defer from blood donation for 4 weeks following yellow fever vaccination to prevent potential transmission of vaccine virus. ​

Tuberculosis testing: Yellow fever vaccine may interfere with tuberculin skin testing (Mantoux test), potentially causing a false-negative result due to transient immune suppression. The vaccine should preferably not be administered in the 4 weeks before tuberculin skin testing. ​

Immunogenicity in specific situations: Oral prednisone or other systemic corticosteroid therapy may reduce immunogenicity of the vaccine and increase risk of serious adverse events. A careful assessment of the need for and timing of vaccination should be made in individuals on immunosuppressive therapy.

Severe systemic reactions: Although rare, severe reactions including encephalitis, meningitis, viscerotropic disease, and anaphylaxis can occur. Healthcare personnel administering vaccine must have immediate access to emergency equipment and medications, including epinephrine 1:1000, oxygen, and resuscitation equipment

Age-related precautions:

Infants 6 to 9 months of age: Vaccination should only be considered when travel to high-risk endemic areas is unavoidable and risk is high. Expert advice is strongly recommended.

Persons aged 60 years and older: Yellow fever vaccination should only be administered following thorough individual risk assessment demonstrating significant and unavoidable risk of acquiring yellow fever infection. Serious adverse events occur at rates of 2.2 cases per 100,000 doses for YEL-AND and 1.2 cases per 100,000 doses for YEL-AVD in this population. The risk of serious adverse events is 3 times higher in those aged 60–69 years and 5 times higher in those aged ≥70 years compared to younger vaccinees.