risks associated with yellow fever vaccination - viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND)
Yellow fever vaccination is a live, attenuated and freeze- dried preparation of the 17D strain of the virus, propagated in chick embryos.
The vaccine is injected within one hour of reconstitution and is given only at designated centres, which can be found listed in "Immunisation against infectious disease". The vaccine is fully effective after 7-10 days (1). The vaccine is effective (95%-100% protection) and immunity persists for 10 years and possibly provides life-long protection. However for the purpose of certification a booster is required every 10 years (1).
This vaccination is contraindicated for various patients:
- those aged five months and under
- those who have had a confirmed anaphylactic reaction to a previous dose of yellow fever vaccine
- those who have had a confirmed anaphylactic reaction to any of the components of the vaccine
- those who have had a confirmed anaphylactic reaction to egg
- those who have a thymus disorder
- patients considered immunocompromised due to a congenital condition, disease process or treatment
- if an individual is acutely unwell, immunisation should be postponed until they have fully recovered. This is to avoid wrongly attributing any new symptoms or the progression of symptoms to the vaccine
- in people over 60 years of age - the risk for neurologic and viscerotropic adverse events increases with age
- yellow fever vaccine should not be given to pregnant women because of the theoretical risk of fetal infection from the live virus vaccine
- breast feeding
- there is some evidence of transmission of live vaccine virus to infants under two months of age from breast milk. As noted earlier, infants aged five months and under should not be immunised and infants aged six to nine months should only be immunised if the risk of yellow fever during travel is unavoidable; expert opinion should be sought in these situations. Therefore, expert advice should be sought from NaTHNaC (www.NaTHNaC.org) or Health Protection Scotland (www.Travax.nhs.uk) before administering yellow fever vaccine to women who are breastfeeding.
- unless the yellow fever risk is unavoidable, asymptomatic HIV-infected persons should not be immunised
Before administration of the yellow fever vaccine, the Summary of Product Characteristics requires that healthcare professionals must ensure that (2):
- Yellow fever vaccination is recommended for the intended destination, based on yellow fever endemic status at the time of the travel or if an International Certificate of Vaccination is required; this information is available from the World Health Organization, NaTHNaC or Public Health Scotland
- The traveller has no contraindication for vaccination (such as acquired or congenital immunosuppression, including thymus disorders or thymectomy for any reason, and known immunosuppressive therapies, or are infants younger than 6 months) – see full contraindications
- They have explored and thoroughly assessed the risk factors and precautions as listed in the section ‘Special warnings and precautions for use’ before vaccine administration (for example, people aged 60 years or older, infants aged 6 months to 9 months, and pregnant or breastfeeding women)
- The traveller is informed of risks associated with vaccination or non-vaccination following the full risk assessment - it is the healthcare professional’s responsibility to ensure the patient understands and accepts the risks before vaccination
- Vaccinees are advised to seek emergency medical attention if they develop signs or symptoms of YEL-AND or YEL-AVD and receive the manufacturer’s Patient Information Leaflet, which lists characteristics of these reactions
The Stamaril Yellow Fever vaccine Checklist supports this consultation (2)
- however it is not a replacement for the full travel health risk assessment currently undertaken by a qualified practitioner.
Additional checklists or materials may also be used prior to vaccination, depending on clinical guidance of the vaccination centre and the national authority (2).
Check up to date version of "The Green Book" before prescribing/administering Yellow fever vaccination.
- an MHRA alert stated "..recently received 2 reports of fatal adverse reactions to the yellow fever vaccine (Stamaril). Due to an increased risk of life-threatening reactions, the vaccine must not be given to anyone with a medical history of thymus dysfunction or who is immunosuppressed. In addition, extreme caution must be used and a careful risk assessment conducted before vaccination of people aged 60 years and older due to a substantially increased risk of such adverse reactions in this age group. .."
- Very rare risks associated with yellow fever vaccine
- 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
- Immunisation Against Infectious Disease - "The Green Book".Chapter 35 Yellow fever
- MHRA. Drug Safety Update volume 15, issue 4: November 2021: 1.
- MHRA (April 2019). Yellow fever vaccine (Stamaril) and fatal adverse reactions: extreme caution needed in people who may be immunosuppressed and those 60 years and older
- MHRA (November 2019). Yellow fever vaccine: stronger precautions in people with weakened immunity and in those aged 60 years or older.
Last edited 05/2022 and last reviewed 05/2022