Yellow fever is a viral disease produced by mosquitoes, and is widespread in sub-Saharan Africa and tropical South America. Responsible for approximately 200,000 cases of clinical disease globally, the yellow fever virus also causes 30,000 deaths annually. Clinical disease ranges from mild febrile illness to severe disease with jaundice and hemorrhage. Because no explicit treatment option exists for patients with yellow fever, preventive vaccination is vital for reducing morbidity and mortality rates. In February 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single dose of yellow fever vaccine provides enduring protection, and is appropriate for most travelers. Notably, the 10-year booster dose requirement will be removed from the International Health Regulations by June 2016; however, booster doses are still recommended for patients at high risk for yellow fever, including those who may not have a robust immune response to the vaccine, laboratory personnel, and certain travelers.
The yellow fever vaccine is recommended for patients aged ≥9 months who live in or are traveling to regions at risk for transmission of the yellow fever virus. The International Health Regulations—which are meant to reduce the potential spreading of the yellow fever virus—allow countries to require proof of yellow fever vaccination from travelers who enter their country. These regulations currently state that 1 dose of yellow fever vaccine is effective for 10 years; therefore, those traveling to countries that require yellow fever vaccination must have received 1 dose of the yellow fever vaccine in the past decade.
Yellow Fever Vaccine Longevity and Efficacy
In April 2013, the World Health Organization Strategic Advisory Group of Experts on Immunization determined that 1 dose of yellow fever vaccine is sufficient for lifelong protection against yellow fever, and that a booster dose is unnecessary. This decision was based on a systematic review of published studies on the duration of immunity 1 dose of yellow fever vaccine affords, and data suggesting that vaccine failures are very rare and do not increase with time from vaccination. The advisory group stated, however, that future studies should be used to identify specific populations who may benefit from a booster dose, such as patients with human immunodeficiency virus (HIV), or infants. In addition, the World Health Assembly approved the recommendation to remove the 10-year booster dose requirement from the International Health Regulations by June 2016 in May 2014.
When assessing the need for booster doses of yellow fever vaccine in US travelers or laboratory workers, the critical benefits considered were vaccine effectiveness (ie, lack of vaccine failure), and evidence of seropositivity (ie, identifying yellow fever virus antibodies in a blood sample). Following the administration of >540 million doses of the yellow fever vaccine, 23 vaccine failures were identified. Five vaccine failures that occurred <10 days postvaccination were excluded, because, in that time frame, most patients are unlikely to develop protective titers. Of the remaining 18 vaccine failures, 16 (89%) happened in patients who received a dose of the vaccine within the past 10 years, and 2 occurred at 20 and 27 years postvaccination, respectively.
Serious adverse events, yellow fever vaccine–associated viscerotropic disease, and yellow fever vaccine–associated neurologic disease were considered critical risks in assessing the necessity of yellow fever vaccine booster doses. Nine observational studies provided data on serious adverse events of 333 million doses of the yellow fever vaccine. A total of 1255 patients experienced a serious adverse event after yellow fever vaccination. For the majority (84%) of patients, it was unknown if the adverse event occurred after a primary or booster dose of the vaccine. Of the 201 patients who had a serious adverse event where their dose type was known, 14 (7%) of the adverse events occurred after a booster dose of the vaccine.
Vaccination of Pregnant Women and Children
The number of pregnant women who develop yellow fever virus antibodies varies; this may be attributed to the trimester in which they receive the vaccine. Among 83 pregnant women who received the yellow fever vaccine in their third trimester, 32 (39%) showed evidence of seroconversion to yellow fever virus at 2 to 4 weeks postvaccination compared with 89 (94%) in the general population. Among 433 pregnant women who received the vaccination in their first trimester, 425 (98%) developed yellow fever virus–specific neutralizing antibodies 6 weeks after receiving the vaccination. In addition, 12 studies of infants and children aged 4 months to 10 years in endemic areas provided data on their initial immune response to the yellow fever vaccine. In 4675 infants and children, the estimated seroconversion rate was 93% (confidence interval, 88%-96%). There was no difference in the seroconversion rates of infants aged <9 months versus those aged ≥9 months. Furthermore, in the past 20 years, 90% of all yellow fever cases occurred in countries in West Africa; epidemiologic data have shown that travelers voyaging to West Africa are at the highest risk for travel-associated yellow fever. Laboratory workers who regularly work with wild-type yellow fever virus, and people traveling to a region with an ongoing outbreak—or to an endemic area for an extended period—are also at high risk for yellow fever virus exposure and disease.
Few vaccine failures are documented after a primary dose of yellow fever vaccine, and most (92%) recipients of primary vaccine sustain detectable levels of neutralizing antibodies ≥10 years postvaccination. In addition, serious adverse events have rarely been reported following a booster dose of the yellow fever vaccine. Based on these data, and because 1 dose of yellow fever vaccine provides long-lasting protection against the yellow fever virus, the ACIP has voted to no longer recommend booster doses of the yellow fever vaccine to most travelers. Additional doses of yellow fever vaccine, however, are recommended for certain patients—eg, pregnant women, hematopoietic stem-cell transplantation recipients, and patients with HIV—who may not have as strong or maintained immune response to the yellow fever vaccine. Furthermore, additional doses may be given to certain people who are at increased risk for yellow fever because of their location, duration of travel, or more consistent exposure to infectious virus.
- Staples JE, Bocchini JA, Rubin L, Fischer M. Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:647-650.