Yellow fever vaccine (Stamaril) and fatal adverse reactions: extreme caution needed in people who may be immunosuppressed and those 60 years and older

We have 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.

Reminder for healthcare professionals:

  • as with any live attenuated vaccine, yellow fever vaccine must not be given to people who may be immunosuppressed

  • yellow fever vaccine is contraindicated in people with a history of thymus dysfunction (including myasthenia gravis and thymoma)

  • yellow fever vaccine is contraindicated in people who have had their thymus gland removed (thymectomy)

  • in people aged 60 years and older, the vaccine should only be given when it is considered that there is a significant and unavoidable risk of acquiring yellow fever infection

  • professionals who administer yellow fever vaccine must be familiar with any contraindications and special precautions before proceeding with immunisation

  • if there is any doubt as to whether a person who is due to receive yellow fever vaccine may be immunosuppressed, immunisation should be deferred until specialist advice has been sought

  • protocols and checklists should be strengthened to avoid inappropriate administration that can lead to severe and possibly fatal adverse effects; those administering the vaccine should also be familiar with the YF Vaccine Centre code of practice

  • any suspected adverse reactions during immunisations should be reported on a Yellow Card

Background

We previously issued advice (see April 2016 Drug Safety Update, and a reminder in November 2017 Drug Safety Update) that live attenuated vaccines should not be given to people who are clinically immunosuppressed (either due to therapy, underlying illness, or pregnancy). This is because live vaccine strains can replicate and cause an extensive, severe, and sometimes fatal infection.

Recent reports of fatal adverse reactions to yellow fever vaccine

In recent months, we have been notified of 2 fatal adverse reactions to yellow fever vaccine. In one case, the vaccine was given to a person with a history of thymectomy following a thymoma (a contraindication in the product information). In another case, the vaccine was given to a 67-year-old with no other known risk factors. Both patients died shortly after vaccination due to suspected yellow fever vaccine-associated viscerotropic disease (YEL-AVD).

YEL-AVD is a recognised adverse reaction that resembles severe yellow fever infection. The global reporting rate is around 1 case in every 1 million people vaccinated, with thymus disease, immunosuppression, and an age of 60 years and older increasing the risk.123 Another serious risk of vaccination is vaccine-associated neurotropic disease (YEL-AND), which can occur at a similar rate and with the same risk factors. YEL-AND can present with a variety of neurological manifestations.

Contraindications and warnings for the yellow fever vaccine

For full prescribing information and warnings, precautions, and risks, please refer to the Summary of Product Characteristics.

Yellow fever vaccine is contraindicated in any person who is immunosuppressed due to immunosuppressive therapy or congenital or idiopathic disease. This includes a history of thymus dysfunction (including myasthenia gravis and thymoma). A history of thymectomy is also a contraindication.

Due to a higher risk of severe and potentially fatal adverse reactions, yellow fever vaccine should only be given to people aged 60 years and older when it is considered that there is a significant and unavoidable risk of acquiring yellow fever infection.

Any healthcare professional prescribing or administering the vaccine must ensure they are fully familiar with the up-to-date Summary of Product Characteristics. More information and guidance on yellow fever vaccine can also be found in the Green Book and the National Travel Health Network and Centre (NaTHNaC) website.

We are in the process of reviewing the benefit-risk balance of yellow fever vaccine and measures to minimise risks in the light of these cases and the latest scientific data. The Commission on Human Medicines has convened an Expert Working Group, which will make recommendations. We will update guidance, as necessary.

Risk assessment at vaccination

When a person presents for yellow fever immunisation, it is important that healthcare professionals clearly discuss with them the individual risks and benefits of the vaccine based on their specific travel itinerary. Sufficient time should be set aside to ensure that the person is immune competent and has no contraindications to the vaccine, including a review of full medical history and any available medical records. Any potential history of thymus disease or thymus removal should be specifically queried. Any decision to administer the vaccine to a person aged 60 years and older must be based on a significant and unavoidable risk of acquiring yellow fever infection.

Provision of the Patient Information Leaflet would provide a helpful basis for this discussion with potential vaccinees. Risk assessment checklists should also be used to ensure checks have been completed and patients have been assessed for immunocompetence (in line with local and organisational requirements).

NaTHNaC recommends that health professionals use a travel risk assessment form to guide the travel health consultation and, where appropriate, seek specialist advice when a significant medical history is identified. More information on yellow fever, and the YF Vaccine Centre code of practice can be found on the NaTHNaC website.

Report suspected adverse reactions to vaccines or medicines

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.

Any medication error (for example, vaccination of a contraindicated patient) that results in harm should be reported via the Yellow Card Scheme. Medication errors in the absence of harm should be reported to NHS England via the National Reporting and Learning System.

Article citation: Drug Safety Update volume 12, issue 9: April 2019: 1.

Published 16 April 2019