What are the contraindications for the yellow fever vaccine?

Contraindications for Yellow Fever Vaccine

Yellow fever vaccine is contraindicated for persons with thymus disorders associated with abnormal immune function, severe immunosuppression (including HIV with CD4 <200/mm³), primary immunodeficiencies, malignant neoplasms, transplantation, and those on immunosuppressive therapies. 1

Specific Contraindications

Thymus Disorders

• Contraindicated in persons with thymus disorders associated with abnormal immune cell function (e.g., thymoma or myasthenia gravis) 1
• 17% of initial yellow fever vaccine-associated viscerotropic disease (YEL-AVD) cases occurred in persons with thymectomies for thymomas 1
• Note: The vaccine can be administered to persons who underwent incidental surgical removal of the thymus or have a remote history of radiation therapy to the thymus 1

HIV Infection and AIDS

• Contraindicated in persons with:
  • AIDS or other clinical manifestations of HIV 1
  • CD4 counts <200 per mm³ or <15% of total lymphocytes for children <6 years 1, 2
• One fatal yellow fever vaccine-associated neurotropic disease (YEL-AND) case has been reported in a person with undiagnosed HIV and CD4 count of 108 cells/mm³ 1
• If travel to endemic areas is unavoidable for these patients, a medical waiver should be provided with emphasis on mosquito bite prevention 1

Other Immunodeficiencies

• Contraindicated for persons with:
  • Primary immunodeficiencies 1
  • Malignant neoplasms 1
  • Solid organ transplant or hematopoietic stem cell transplant recipients within 2 years of transplantation 1
  • Transplant recipients >2 years post-transplant who are still taking immunosuppressive drugs 1

Immunosuppressive and Immunomodulatory Therapies

• Contraindicated for persons on:
  • High-dose systemic corticosteroids (≥2 mg/kg body weight or ≥20 mg/day of prednisone or equivalent for ≥2 weeks) 1
  • Alkylating drugs 1
  • Antimetabolites 1
  • TNF-α inhibitors (e.g., etanercept) 1
  • IL-1 blocking agents (e.g., anakinra) 1
  • Monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab) 1
• Note: Corticosteroids are NOT a contraindication when administered:
  • Short-term (<2 weeks)
  • Low-to-moderate dose (<20 mg prednisone or equivalent daily)
  • Alternate-day treatment with short-acting preparations
  • Maintenance physiologic doses
  • Topically, inhaled, or by intra-articular injection 1

Age-Related Contraindications

• Infants <6 months of age 1
• Rates of YEL-AND are substantially elevated in infants <6 months (50-400 cases per 100,000 infants vaccinated) 1

Precautions (Not Absolute Contraindications)

Age-Related Precautions

• Infants 6-8 months of age 1
• Adults ≥60 years of age, particularly for first dose 1
  • Increased risk of serious adverse events (8.3 events per 100,000 doses vs. 4.7 events per 100,000 doses for all recipients) 1

Pregnancy

• Yellow fever vaccine should generally not be administered to pregnant women, except if travel to an endemic zone is unavoidable 3

Clinical Decision-Making Algorithm

1. Assess immune status:

   • Check for thymus disorders, HIV status with CD4 count, primary immunodeficiencies, malignancies, transplant history
   • Review medication list for immunosuppressive drugs

2. Assess age:

   • Absolute contraindication: <6 months
   • Precaution: 6-8 months or ≥60 years

3. If contraindicated but travel to endemic area is unavoidable:

   • Provide medical waiver
   • Emphasize protective measures against mosquito bites
   • Consider alternative travel destinations

4. For patients with HIV but CD4 >200/mm³:

   • Yellow fever vaccine may be considered if travel to endemic areas is necessary 2, 4
   • Monitor for adverse events

Important Considerations

• The risk-benefit assessment is critical when considering yellow fever vaccination in patients with relative contraindications who must travel to endemic areas 1
• Patients with contraindications who receive a medical waiver should be counseled that they remain at risk for yellow fever infection 1
• While some studies suggest that HIV-infected patients with CD4 counts >200/mm³ can safely receive the vaccine, they may develop lower concentrations of neutralizing antibodies compared to uninfected individuals 4, 5