Yellow fever, live attenuated

Animal reproduction studies have not been conducted with Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection). It is also not known whether Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) should be given to a pregnant woman only if clearly needed.

Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) has not been evaluated in pregnant women. However, based on experience of other yellow fever vaccines, the following findings have been determined for safety and effectiveness. A case-control study of Brazilian women found no significant difference in the odds ratio of spontaneous abortion among vaccinated women compared to a similar unvaccinated group. In a separate study in Trinidad, 100 to 200 pregnant females were immunized, no adverse events related to pregnancy were reported. In addition, 41 cord blood samples were obtained from infants born to mothers immunized during the first trimester. One of these infants tested positive for IgM antibodies in cord blood. The infant appeared normal at delivery, and no subsequent adverse sequelae of infection were reported. However, this result suggests that transplacental infection with 17D vaccine viruses can occur. In another study involving 101 Nigerian women, the majority of whom (88%) were in the third trimester of pregnancy, none of the 40 infants who were delivered in a hospital tested positive for IgM antibodies as a criterion for transplacental infection with vaccine virus. However, the percentage of pregnant women who seroconverted was reduced compared to a non-pregnant control group (38.6% vs. 81.5%).

Because of the potential for serious adverse reactions in nursing infants from Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection), a decision should be made whether to discontinue nursing or not to administer the vaccine, taking into account the importance of the vaccine to the mother. As of July, 2015, three vaccine-associated neurotropic disease cases have been reported worldwide in exclusively breastfed infants whose mothers were vaccinated with yellow fever vaccines, including one case reported after vaccination with Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection). All three infants were diagnosed with encephalitis and were less than one month of age at the time of exposure. Because age less than 9 months is a risk factor for yellow fever vaccine-associated neurotropic disease, Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) is contraindicated in lactating women who are providing breastmilk to infants younger than 9 months of age. Discuss the risks and benefits of vaccination with lactating women who are providing breastmilk to infants 9 months of age and older.

Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) has not been evaluated for its carcinogenic or mutagenic potential or its effect on fertility.

Data from Clinical Studies

Adverse reactions to Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) 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 Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection). 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. Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) was used as a control in a double-blind, randomized comparative trial with another 17D-204 vaccine, conducted at nine centers in the US. Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) 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 Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection), 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.

Data from Post-marketing Experience

The following additional adverse events have been spontaneously reported during the post-marketing use of Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) 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 Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection).

General disorders and administration site conditions

Injection-site blisters

Immune System Disorders

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

Isolated cases of Yellow Fever Vaccine-Associated Neurotropic Disease (YEL-AND), sometimes fatal, have been reported to occur within 30 days following vaccination with Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection), and other yellow fever vaccines. Age less than 9 months and congenital or acquired immunodeficiency have been identified as risk factors for this event. 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 vaccine-associated 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. A study in Senegal 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.

Other neurological complications have included Guillain-Barré 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 Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) and other yellow fever vaccines. 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. 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. Age older than 60 has also been identified as a risk factor for this event. 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 YFVAX vaccine. Three of these 4 subjects died. The incidence rate for these serious adverse events was estimated at 1 per 400,000 doses of Yellow Fever Vaccine (yellow fever virus strain 17d-204 live antigen injection) vaccine, based on the total number of doses administered in the U.S. civilian population during the surveillance period. YEL-AVD has occurred after yellow fever vaccination in fewer than 1:100,000 U.S. vaccinees, 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).