Sandra Adamson Fryhofer, MD


March 17, 2015

In This Article

Yellow Fever Revaccination Conundrum Resolved

Yellow fever (YF) is a mosquito-borne flavivirus that is endemic to sub-Saharan Africa and tropical South America. The risk for infection in West Africa during peak transmission season is about 10 times higher than the risk for acquisition in South America. Although most cases in humans are asymptomatic, the World Health Organization (WHO) says that YF is to blame for more than 200,000 clinically apparent cases and at least 30,000 deaths worldwide each year.[3]

Since 1965, international health regulations have allowed countries to require YF vaccination within the previous 10 years as criteria for entry. Requiring proof of vaccination is at the country's discretion. In April 2013, a WHO Strategic Advisory Group of Experts (SAGE) concluded that a single dose of yellow fever vaccine provided lifelong immunity.[4] In May 2014, the WHO Health Assembly adopted an amendment that extends YF vaccine protection to the lifetime of the vaccinated person. The legal effective date of this international health regulation is June 2016.[5]

The ACIP's YF Working Group GRADE analysis of the revaccination data was presented at the June 2014 ACIP meeting. The working group also concluded that a single dose of YF vaccine should provide lifelong immunity for most travelers and proposed no longer recommending booster doses. However, the ACIP did not view this as an easy decision. After much discussion and many questions, no ACIP vote was taken.[6] This topic was discussed again at the February 2015 ACIP meeting after a thorough systematic literature review including 32 published studies, as well as some unpublished data from the CDC, the Vaccine Adverse Event Reporting System (VAERS), and the Brazil Ministry of Health.[7]

Risks and Benefits of YF Vaccination

The YF vaccine has a good track record of effectiveness. Of the more than 540 million doses of YF vaccine administered, there have been only 18 documented vaccine failures.[7]

The most common side effects after vaccination include mild headache, muscle ache, and low-grade fever, in addition to redness, pain, and swelling at the injection site.[3] More serious adverse events after YF vaccination include multiple organ system failure known as viscerotropic disease (abbreviated YEL-AVD), as well as severe neurologic sequelae (abbreviated YEL-AND), which include meningoencephalitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and bulbar palsy.[3]

The risk for serious adverse events is increased in infants aged less than 8 months (YF vaccine is contraindicated for infants younger than 6 months), adults aged 60 years or older, and persons with altered immune systems.[3] Pregnancy and breastfeeding are considered precautions to YF vaccination.[7] Data show that some pregnant women do not seroconvert after initial vaccination. Data also show that HIV-infected persons do not always have sustained YF virus-specific titers after initial vaccination.[7] All of these variables were considered in the ACIP's evidence-based evaluation and led to a shift in YF vaccination recommendations.[7]

New YF Vaccine Recommendations

After evidence-based data review, the ACIP concurred with WHO's SAGE group of advisors and determined that a single dose of YF vaccine provides long-lasting protection and no longer recommends booster doses for most travelers. However, there are a few exceptions.[7] Booster doses of YF vaccine should still be recommended or at least considered for the following groups of travelers[7]:

  • Female travelers who were pregnant when they received their first YF vaccine dose;

  • Travelers who were HIV-infected when they received their last dose;

  • Stem cell transplant recipients (when immunocompetent) who were vaccinated before transplant; and

  • Travelers at least 10 years from their last YF dose who are planning to spend a prolonged period in a highly endemic area (such as rural West Africa) during peak transmission season or during an ongoing outbreak.

In addition, laboratory workers who handle wild-type YF virus need to either have a 10-year YF booster or have YF-specific neutralizing antibody titers checked (which can be done only by the CDC) every 20 years.


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