Yellow fever vaccine: stronger precautions in people with weakened immunity and in those aged 60 years or older
The Commission on Human Medicines has issued a series of recommendations to strengthen measures to minimise risk with the yellow fever vaccine (Stamaril) following very rare fatal reactions. Key recommendations include new and updated contraindications and strengthened precautions to protect those with a weakened immune systems (including for people aged 60 years or older) and standardised risk-benefit evaluation procedures across UK yellow fever vaccination centres to ensure that people only receive the vaccine after a thorough risk assessment.
Post-publication note: November 2021
In 2019, the Commission on Human Medicines (CHM) issued a series of recommendations to strengthen measures to minimise risk with the yellow fever vaccine (Stamaril) following very rare fatal reactions. These were communicated in a Drug Safety Update article in November 2019. Following the CHM recommendations, in November 2021 a standardised pre-vaccination checklist was introduced for practitioners in vaccination consultations to ensure systematic evaluation of benefits and risks for individual travellers. See Drug Safety Update, November 2021 for more information.
Advice for healthcare professionals:
- yellow fever vaccine is a highly effective vaccine to protect against life-threatening yellow fever infection; however, strict adherence to contraindications and precautions is essential to reduce the risk of very rare but potentially fatal adverse reactions
- following a review of the benefits and risks of the vaccine, the Commission on Human Medicines (CHM) has made recommendations to strengthen measures to minimise risk
- key recommendations include new and updated contraindications, strengthened precautions for use in individuals aged 60 years and older, and standardised risk-benefit evaluation procedures across UK yellow fever vaccination centres to ensure that people only receive the vaccine after a thorough risk assessment
- a letter from MHRA, Public Health England, National Travel Health Network and Centre (NaTHNaC), and Health Protection Scotland has been sent to UK yellow fever vaccination centres to inform them of the recommendations and that changes will be made to the product information and standardised pre-vaccination screening tools
- only healthcare professionals specifically trained in benefit-risk evaluation of yellow fever vaccine should administer the vaccine, following their individualised assessment of a person’s travel itinerary and suitability to receive the vaccine
- every vaccinee should be advised to seek emergency medical attention if they develop signs or symptoms of very rare neurotropic disease (YEL-AND) or viscerotropic disease (YEL-AVD) and should receive the manufacturer’s patient information leaflet as part of the travel consultation
Yellow fever vaccine
Yellow fever is a life-threatening viral infection and protective measures against the disease are essential for anyone travelling to an area where there is a risk of infection. Yellow fever vaccine (Stamaril) is highly effective and is the best way to protect those at risk of disease during travel.
For most people, the balance between the benefits and possible side effects of the vaccine remains overwhelmingly favourable. However, because the vaccine contains a live, weakened strain of the yellow fever virus, strict adherence to contraindications and precautions is essential to reduce the risk of serious side effects in those who may have a weaker immune system.
Revaccination is generally not recommended as the duration of protection following administration of 1 dose of yellow fever vaccine is expected to be lifelong.
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-Barré 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.
Trigger for detailed review and recommendations
Recent fatal cases of YEL-AVD in the UK prompted the UK’s Commission on Human Medicines (CHM) to convene an Expert Working Group in 2019 to consider the balance of benefits and risks of yellow fever vaccine, risk factors for serious adverse reactions, and the measures in place in the UK to minimise risks. While the review was ongoing, advice to healthcare professionals was issued that extreme caution was needed in people who were immunosuppressed and in people aged 60 years and older (see Drug Safety Update April 2019).
The review considered published data and vaccine adverse events reported to the MHRA, the manufacturer, and incidents reported through National Travel Health Network and Centre (NaTHNaC) and Health Protection Scotland (HPS). A full report of the review and evidence base for the recommendations is available.
This review concluded in October 2019, and CHM has now issued a set of updated recommendations to minimise risks to vaccinees. The recommendations are in addition to the full list of contraindications and precautions described in the current Summary of Product Characteristics and Patient Information Leaflet, which will be updated. Standardised pre-vaccination screening checklists are also being produced, along with a patient group direction template. A further communication will be issued once these documents are ready to ensure they can be implemented in clinical practice.
The key recommendations of the review can be found in the sent to vaccination clinics on 21 November 2019.
Background
More than 600 million doses of yellow fever vaccine have been used worldwide since the 1930s. Stamaril (Sanofi Pasteur) is the only licensed yellow fever vaccine available in the UK.
Report suspected reactions to vaccines
Please continue to report suspected adverse reactions to vaccines and other medicines to the Yellow Card scheme. When reporting a suspected reaction to a vaccine, please provide the brand name (or product licence number and manufacturer) and the specific batch number. Additionally, when providing patients with details of the vaccine administered, it is good practice to give them details of the brand and batch number. This will allow patients and carers to more accurately report suspected reactions to the Yellow Card scheme.
Incidents involving the yellow fever vaccine in England, Wales, and Northern Ireland should be reported to NaTHNaC and incidents in Scotland should be reported to HPS.
Any medication error (for example, vaccination of a contraindicated person) that results in harm should be reported via the Yellow Card scheme. Medication errors in the absence of harm should be reported via local reporting methods
Article citation: Drug Safety Update volume 13, issue 4: November 2019: 1.