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Safety of inactivated influenza vaccines

The influenza vaccines currently used in New Zealand are inactivated. They do not contain live viruses (1-3) and cannot cause influenza. FLUAD QUAD contains an adjuvant, MF59, to enhance the person’s immune response to the vaccine. (1) The AFLURIA QUAD, AFLURIA QUAD JUNIOR and FLUQUADRI vaccines do not contain an adjuvant. (2,3) 

MF59 is a squalene-based oil-in-water adjuvant that has been used in influenza vaccines since 1997. Although squalene is produced naturally in the human body, the squalene used in the vaccine comes from shark liver. Squalene is also used during the manufacture of food, cosmetics, and medicines. MF59 in influenza vaccines has an excellent safety record. (4) 

Influenza vaccination does not increase the risk of being infected with the SARS-CoV-2 (COVID-19) virus or any other respiratory virus. A U.S. study of people presenting for medical care with a respiratory illness from 2010 to 2013 found that influenza vaccination reduced the risk of influenza disease and had no effect on the risk of other respiratory viruses. (5) Analysis of medically attended influenza-like illnesses over seven influenza seasons, from 2010 to 2017 in Canada, also showed that influenza vaccination reduced the risk of influenza and did not have an effect on illnesses caused by other respiratory viruses, including coronaviruses. (6)

Common responses to vaccination

Influenza vaccine is generally well tolerated. Some systemic responses to vaccination may appear influenza-like. However, inactivated vaccines cannot cause the disease.Common responses associated with the non-adjuvanted influenza vaccines (AFLURIA QUAD and AFLURIA QUAD JUNIOR) in children and adults include pain, redness, and/or swelling at the site of injection. Local responses are almost always mild. Systemic responses such as headache, muscle aches and fatigue may occur in adults. (7,8) Fever, irritability and loss of appetite are more likely to occur in children. (9,10) These are generally mild and usually resolve after a day or so. Systemic events may appear influenza-like. 

Adults aged 65 years or older are more likely to experience local and/or systemic responses to the adjuvanted in influenza vaccine FLUAD QUAD than the non-adjuvanted AFLURIA QUAD vaccine (11-13) because the adjuvant enhances the person’s immune response. (12,14)

Common responses associated with FLUAD QUAD in adults aged 65 years or older include injection site warmth, (11) tenderness/pain, (11-13) swelling, (13) and/or itching (13) at the site of injection. Systemic responses such as fatigue, (11-13) feverishness, (13) nausea, (13) muscle aches, (11,12) and/or headache (11,12) may also occur. Generally, the vaccine responses are mild to moderate. (12,13) Injection site pain and swelling, and fatigue, feverishness and/or nausea typically resolve more quickly in adjuvanted vaccine recipients during the 4 days after vaccination compared with those who receive a non-adjuvanted vaccine. (12,13)

Serious events associated with influenza vaccine

The most significant serious adverse event associated with influenza vaccination is anaphylaxis, a serious allergic response that usually comes on within minutes of receiving the vaccine. This occurs around once in a million influenza vaccine doses. (15)

Vaccine-related serious adverse events, such as a convulsion associated with fever or cellulitis-like local reaction, are rare. (16-18)

Guillain-Barre Syndrome and influenza vaccination

Guillain-Barré syndrome (GBS) has an annual incidence of around 1–4 cases per 100,000 people worldwide. (19)

During a swine influenza vaccination campaign in the U.S. in the 1970s, an increase in GBS was observed in vaccine recipients (around one case per 100,000 vaccinations) and the vaccination campaign was halted and surveillance of GBS expanded. (20)

Epidemiological studies since then have suggested either no increased risk or a possible slight increase in risk of around one case per million adult influenza vaccinations. A meta-analysis of these studies identified a small increase in the risk of GBS following influenza vaccination. (21) However, studies have also identified that the risk of GBS following an episode of influenza-like-illness is significantly higher than the risk following influenza vaccination, especially in older adults. (22,23) This highlights the importance of balancing the potential risks of disease with the potential risks and benefits of influenza vaccination to make an informed decision. (24)

Febrile events following influenza vaccination

Fever is a common adverse event in children after vaccination. (9,10) Convulsions associated with fever can occur in susceptible children. Around 3–8 children in 100 aged under 7 years will experience a febrile convulsion, most likely when aged between 16 and 30 months. (25)
In one study, children aged 6–23 months were two to three times more likely to develop a fever of 38°–39°C during the first 24 hours after receiving influenza and PCV13 (PREVENAR 13®) vaccines at the same visit compared with children who received the vaccines on separate days. (26) 

Parents/guardians whose children are recommended to receive both influenza vaccine and PCV13 should be advised of the possible increase in risk of fever following concurrent administration of these vaccines. Separating administration of these vaccines by 2 days can be offered but is not essential.

Reporting adverse events following influenza vaccination

Healthcare professionals/vaccinators are professionally and ethically responsible for reporting any serious or unexpected adverse events after the administration of all medicines, including the influenza vaccine, regardless of whether or not they consider the event to have been caused by the vaccination.

Information should include:

  • vaccinee’s details
  • the vaccine administered
  • vaccine batch number
  • date of onset of symptoms
  • type and duration of adverse event
  • treatment required
  • outcome if known but do not delay reporting while waiting outcome information

Some providers are able to report events through their practice management system. Reports can be completed online (nzphvc.otago.ac.nz), or the form can be downloaded and printed using the above link, completed and mailed to:

Freepost 112002
The Medical Assessor
Centre for Adverse Reactions Monitoring
University of Otago Medical School
PO Box 913, Dunedin 9054
or faxed to: (03) 479 7150

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