Yellow Fever Vaccine Side Effects Center

SIDE EFFECTS

Data From Clinical Studies

Adverse reactions to YF-VAX include mild headaches, myalgia, low-grade fevers, or other minor symptoms for 5 to 10 days. Local reactions including edema, hypersensitivity, pain or mass at the injection site have also been reported following yellow fever vaccine administration. Immediate hypersensitivity reactions, characterized by rash, urticaria, and/or asthma, occur principally among persons with histories of allergy to eggs or other substances contained in the vaccine.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

No placebo-controlled trial has assessed the safety of YF-VAX. However, between 1953 and 1994, reactogenicity of 17D-204 vaccine was monitored in 10 uncontrolled clinical trials. The trials included a total of 3,933 adults and 264 infants greater than 4 months old residing in Europe or in yellow fever endemic areas. Self-limited and mild local reactions consisting of erythema and pain at the injection site and systemic reactions consisting of headache and/or fever occurred in a minority of subjects (typically less than 5%) 5 to 7 days after immunization. In one study involving 115 infants age 4 to 24 months the incidence of fever was as high as 21%. Also in this study, reactogenicity of the vaccine was markedly reduced among a subset of subjects who had serological evidence of previous exposure to yellow fever virus. Only two of the ten studies provided diary cards for daily reporting; this method resulted in a slightly higher incidence of local and systemic complaints. YF-VAX was used as a control in a double-blind, randomized comparative trial with another 17D-204 vaccine, conducted at nine centers in the US. YF-VAX was administered to 725 adults ≥ 18 years old with a mean age of 38 years. Safety data were collected by diary card for days 1 through 10 after vaccination and by interview on days 5, 11, and 31. Among subjects who received YF-VAX, there were no serious adverse events, and 71.9% experienced non-serious adverse events judged to have been related to vaccination. Most of these were injection site reactions of mild to moderate severity. Four such local reactions were considered severe. Rash occurred in 3.2%, including two subjects with urticaria. Systemic reactions (headache, myalgia, malaise, and asthenia) were usually mild and occurred in 10% to 30% of subjects during the first few days after vaccination. The incidence of non-serious adverse reactions, including headache, malaise, injection site edema, and pain, was significantly lower in subjects > 60 years compared to younger subjects. Adverse events were less frequent in the 1.7% of vaccinated subjects who had pre-existing immunity to yellow fever virus, compared to those without pre-existing immunity. (8)

Data From Post-marketing Experience

The following additional adverse events have been spontaneously reported during the post-marketing use of YF-VAX worldwide. Because these events are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or establish a causal relationship to vaccine exposure. This list includes adverse events based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to YF-VAX.

• Immune System Disorders (14)
  Immediate hypersensitivity reactions or anaphylaxis, characterized by rash and/or urticaria and/or respiratory symptoms (e.g., dyspnea, bronchospasm, or pharyngeal edema) occur principally among persons with histories of allergies to egg or other substances contained in the vaccine.
• Nervous System Disorders(1) (32) (33) (34)
  Isolated cases of Yellow Fever Vaccine-Associated Neurotropic Disease (YEL-AND), sometimes fatal, have been reported to occur within 30 days following vaccination with YF-VAX, and other yellow fever vaccines (see WARNINGS section, Yellow fever vaccine-associated neurotropic disease subsection). Age less than 9 months and congenital or acquired immunodeficiency have been identified as risk factors for this event. (See WARNINGS and CONTRAINDICATIONS sections.) Twenty-one cases of YEL-AND associated with all licensed 17D vaccines have been reported between 1952 and 2004. Eighteen of these cases were in children or adolescents. Fifteen of these cases occurred prior to 1960, thirteen of which occurred in infants 4 months of age or younger, and two of which occurred in infants six and seven months old. The incidence of vaccineassociated neurologic disease in infants less than 4 months old is estimated to be between 50 and 400 cases per 1,000,000, based on two historical reports where denominators are available. (33) (34) (35) A study in Senegal (34) described two fatal cases of encephalitis possibly associated with 17D-204 vaccination among 67,325 children between the ages of 6 months and 2 years, for an incidence rate of 3 per 100,000. The incidence of YEL-AND in the United States is less than 1:100,000 doses administered. (17)
  Other neurological complications have included Guillain-Barre syndrome (GBS), acute disseminated encephalomyelitis (ADEM), and bulbar palsy.
• Infections and infestations
  Isolated cases of Yellow Fever Vaccine-Associated Viscerotropic Disease YEL-AVD, formerly described as “Febrile Multiple Organ-System-Failure”), sometimes fatal, have been reported following YF-VAX and other yellow fever vaccines (see WARNINGS section, Yellow fever vaccine-associated viscerotropic disease subsection). In the majority of cases reported, the onset of signs and symptoms was within 10 days after the vaccination. Initial signs and symptoms are non-specific and may include pyrexia, myalgia, fatigue and headache, potentially progressing quickly to liver and muscle cytolysis and possibly to thrombocytopenia, lymphopenia and acute renal failure.(18) The pathophysiological mechanism of such reactions has not been established. In some individuals with YEL-AVD a medical history of thymic disease has been reported. (36) Age older than 60 has also been identified as a risk factor for this event. (9) During surveillance in the U.S. between 1996 and 1998, four individuals (ages 63, 67, 76, and 79) became severely ill 2 to 5 days after vaccination with YF-VAX vaccine. Three of these 4 subjects died. The incidence rate for these serious adverse events was estimated at 1 per 400,000 doses of YF-VAX vaccine, based on the total number of doses administered in the U.S. civilian population during the surveillance period. (21) YEL-AVD has occurred after yellow fever vaccination in fewer than 1:100,000 U.S. vaccinees, (14) most commonly in individuals 60 years of age and older.

In a CDC analysis of data submitted to the Vaccine Adverse Events Reporting System (VAERS) between 1990 and 1998, the rate of systemic adverse events following vaccination was 2.5-fold higher in the 65 years or older age group (6.2 events per 100,000 doses of vaccine) compared to the 25 to 44 year-old age group (2.5 events per 100,000 doses of vaccine). (31)

Reporting Of Adverse Events

To report SUSPECTED ADVERSE REACTIONS, contact the Pharmacovigilance Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or https://vaers.hhs.gov.

Read the entire FDA prescribing information for Yellow Fever Vaccine (Yellow Fever Vaccine)