Side effects

• adverse reactions following yellow fever vaccine are typically mild and consist of headache, myalgia, lowgrade fever and/or soreness at the injection site and will occur in 10-30% of recipients
  • injection site reactions tend to occur from days one to five after immunisation
  • systemic side effects also occur early but may last up to two weeks
    • reactions are more likely to occur in persons who have no prior immunity to yellow fever virus
    • rarely rash, urticaria, bronchospasm and anaphylaxis occur
      • rate of anaphylaxis following yellow fever vaccine has been estimated to be one case per 130,000 doses of vaccine
        • reactions are most likely related to egg protein in the vaccine
          • possible that some persons are sensitive to and react to the gelatin that is used as a stabilizer in this vaccine as well as in other vaccines
    • post-vaccine encephalitis has been recognised as a rare event since the early use of the vaccine
      • was particularly seen in infants with early reports indicating an incidence of 0.5 to 4 cases per 1000 infants under six months of age
      • since 2001, a new pattern of neurologic adverse events was recognized that occurred in older individuals
        • these events have now been termed yellow fever vaccine-associated neurologic disease (YEL-AND)
        • clinical presentation of this new pattern of neurologic events began four to 23 days following receipt of vaccine with the onset of fever and headache that may progress to include one or more of confusion, focal neurologic deficits, coma and Guillain-Barré syndrome
        • clinical course is usually complete recovery
        • all cases have occurred in primary vaccinees who have no underlying yellow fever immunity
    • yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a newly recognised syndrome of fever and multi-organ failure which resembles severe yellow fever
      • two to seven days following vaccination, patients develop fever, malaise, headache and myalgias that progress to hepatitis, hypotension and multi-organ failure; death has occurred in more than 60% of reported cases
      • as with YEL-AND, all cases have occurred in primary vaccinees without underlying yellow fever immunity
      • in the reports of viscerotropic disease, 17% have had a history of thymus disease with subsequent thymectomy - therefore all patients with thymus disorders should not receive vaccine
    • estimated the risk of neurologic disease to be about four cases per million doses and viscerotropic disease to be three cases per million doses
• Very rare risks associated with yellow fever vaccine (2)
  • two risks unique to yellow fever vaccine are viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND), which both resemble yellow fever infection. These are very rare but can be fatal. At vaccination all vaccinees should receive the manufacturer's patient information leaflet for Stamaril vaccine, which advises them on symptoms to be vigilant for following vaccination
  • these risks are more likely to occur in certain groups, particularly people with a weakened immune system, people without a thymus, and people aged 60 years or older. The risks of YEL-AND and YEL-AVD are estimated to be up to 1 per 100,000 primary vaccinees, although this may be up to 4- times greater in those aged 60 years or older
  • Presentation of YEL-AND
    • cases of neurotropic disease (YEL-AND) have been reported in primary vaccinees with an onset within 30 days of vaccination. The risk appears to be higher in people older than 60 years and younger than 9 months of age (including infants exposed to vaccine through breastfeeding), although cases have been also reported in other age groups. Congenital or acquired immunodeficiency has also been recognised as a potential risk factor
    • YEL-AND may manifest as high fever with headache that may progress to include 1 or more of confusion, lethargy, encephalitis, encephalopathy, and meningitis. Other neurological signs and symptoms have been reported and include convulsions, Guillain-Barre syndrome, and focal neurological deficits
  • Presentation of YEL-AVD
    • cases of viscerotropic disease (YEL-AVD; formerly described as febrile multiple organ-system failure) have been reported following vaccination with yellow fever vaccine, some of which have been fatal. In most cases reported, the onset of signs and symptoms was within 10 days of vaccination
    • initial signs and symptoms of AVD are non-specific and may include pyrexia, myalgia, fatigue, headache and hypotension, potentially progressing quickly to liver dysfunction with jaundice, muscle cytolysis, thrombocytopenia, and acute respiratory and renal failure

Reference:

1. Immunisation Against Infectious Disease - "The Green Book".Chapter 35 Yellow fever
2. MHRA (November 2019). Yellow fever vaccine: stronger precautions in people with weakened immunity and in those aged 60 years or older.