F Letter

Background

One in 30 children will have a febrile seizure at some point during their childhood. They are typically triggered by a sudden rise in temperature, often as a result of a febrile illness. Febrile seizures more commonly occur in children between the ages of six months and six years, with a peak incidence identified between 14-18 months of age.

Febrile seizures can be classified as simple or complex. Simple febrile seizures are most common and are generalised tonic-clonic, lasting less than 15 minutes’ duration, do not recur within 24 hours and there is complete recovery within 1 hour. Complex febrile seizures include seizures with any of the following features: duration longer than 15 minutes, focal or partial features, recurrence within 24hrs or incomplete recovery within 1 hour [see Table 1 below for more details].

After one febrile seizure from any cause, around 1 in 3 children will go on to experience further febrile seizures during childhood. Overall outcomes are excellent and the majority of children who experience febrile convulsions do not experience seizures beyond the age of five.

Seizures following vaccination

Seizures have been described following a number of childhood vaccines, including both inactivated (e.g. influenza) and live attenuated (e.g. measles-mumps-rubella [MMR]) vaccines.

Seizures that occur within 14 days of vaccination are called vaccine-proximate seizures. Vaccine-proximate febrile seizures should be differentiated from vaccine-proximate afebrile seizures and vaccine-proximate status epilepticus.

Vaccine-proximate febrile seizures

Fever is a common side effect following vaccination with certain vaccines eg. meningococcal B, COVID-19, MMR, MMRV and influenza. Fever generally occurs within 48hrs of inactivated vaccines and 5-14 days after administration of live-attenuated vaccines.

Although vaccines can cause fevers, febrile seizures are not common after vaccination. Vaccine-proximate febrile seizures are not more severe than febrile seizures from other causes and the neurodevelopmental outcomes are the same.

It is important to note that infection with vaccine-preventable illnesses can also cause febrile seizures.

Vaccine-proximate status epilepticus and afebrile seizures

Vaccine-proximate status epilepticus and vaccine-proximate afebrile seizures are uncommon. Status epilepticus is a seizure lasting ≥ 30 minutes or multiple seizures over ≥30 minutes without recovery of consciousness between each seizure. Afebrile seizures are seizures occurring in the absence of fever. Children who experience vaccine-proximate status epilepticus or afebrile seizures should be referred to a specialist immunisation clinic. Some children with epilepsy including Dravet syndrome  or genetic epilepsy with febrile seizures (GEFS+) may present with their first seizure in this way.

For further information please refer to MVEC: Epilepsy.

Recommendations

Prophylactic paracetamol

It is widely recognised that children receiving Bexsero (meningococcal B vaccine) are more likely to experience fevers following vaccination. It is for this reason that children < 4 years of age are recommended to receive prophylactic paracetamol prior to vaccination, as well as 2 subsequent doses (6 hours apart) to reduce the likelihood and severity of fever. This should be administered regardless of whether the child is experiencing a fever or not.

MMRV

Measles-mumps-rubella-varicella (MMRV) vaccines are not recommended as a first dose of an MMR- containing vaccine in children < 4 years of age due to the increased risk of fever and febrile seizures. Should MMRV vaccines be inadvertently administered as the first dose of an MMR-containing vaccine, the child’s parent should be counselled to monitor for fevers and administer paracetamol as required. This vaccine administration error should also be reported to SAEFVIC.

Vaccine setting

Children with a history of vaccine-proximate simple febrile seizures or seizures from other causes can be safely vaccinated in the community.  A referral to a specialist immunisation clinic may be considered on a case-by-case basis. [See Table 1 below for different types of vaccine-proximate seizures and vaccine management plans]

Children with vaccine-proximate complex febrile seizures, vaccine-proximate status epilepticus and vaccine-proximate afebrile seizures should be referred to a specialist immunisation clinic for assessment before receiving further vaccinations. These seizures should also be reported to your local vaccine safety service, in Victoria, this is SAEFVIC.

Table 1: Vaccine-proximate seizures and plan for future vaccines

*Table adapted from Deng, L et. al, Seizures Following Vaccination in Children AJGP Vol 49, No 10, October 2020

Summary

Febrile seizures are common in childhood and less commonly occur following vaccination. Children with vaccine-proximate simple febrile seizures and febrile seizures from other causes can safely continue to receive vaccines in the community. Children with vaccine-proximate complex febrile seizures, status epilepticus or afebrile seizures should be referred to a specialist immunisation clinic prior to receiving further vaccinations. In any child with a history of seizures, referral to a specialist immunisation clinic can be considered when there are questions or concerns about the safety of vaccination.

Resources

• CDC: Febrile seizures follwoing childhood vaccinations, including influenza vaccination
• Epilepsy Foundation: Febrile seizures
• Deng, L et. al, Seizures Following Vaccination in Children AJGP Vol 49, No 10, October 2020
• RCH Clinical Practice Guidelines: Febrile seizure
• RCH Kids Health Information: Febrile seizures
• Deng L, et. al, Postvaccination Febrile Seizure Severity and Outcome AAP Vol 143, Issue 5, May 2019

MVEC supports all scientific efforts to rapidly develop safe and effective SARS CoV-2 vaccine(s). This includes technology developed over 50 years ago and has been a proven way to support the production of viral vaccines that have saved so many lives around the world.

Background

In the early 1960’s foetal embryo fibroblast cells were first obtained from 2 elective terminations of pregnancy in order to grow vaccine viruses. These same cell lines have continued to grow in laboratory conditions since this time and have been used in the development of various vaccines including rubella, measles, hepatitis A and rabies vaccines.

How is foetal tissue used in vaccine development?

Vaccine viruses are grown within foetal cell lines because they are human and will mimic how viruses will act when infecting a human host. They can be sustained over time and have been shared by multiple vaccine researchers and developers and are clearly outlined to regulatory authorities, such as the Therapeutic Goods Administration (TGA) in Australia and the Food and Drug Administration (FDA) in America.

There are three current SARS CoV-2 vaccine candidates that have used this technology as part of their development.  They are the Oxford AstraZeneca (UK); Johnson and Johnson (Jansen research US) and CanSino biologics (China). All of these vaccines are in the class called ‘Virus vectors’ and use an adenovirus (common human virus) to help carry the DNA of the SARS CoV-2 spike protein, the part of the virus researchers are targeting to produce a protective immune response.

Why don’t we try to use vaccines without these foetal embryonic cell lines?

The SARS CoV-2 pipeline is progressing at pandemic speed and it was important to utilise proven technologies to support vaccine development. Replication of viruses in the laboratory can be difficult, so these established platforms, as detailed above, is scientifically justifiable There is also a hypothetical concern for transmission of animal diseases if animal embryonic cell lines were to be used for this purpose.

It is also uncertain how many of the SARS CoV-2 vaccines will be shown to be safe and effective, so given the impact of the pandemic and lives that may be saved by vaccine(s), we should be open to discussing these products and addressing ethics issues that are being raised as part of COVID-19 vaccine readiness planning.

Religious and ethical implications

Even though foetal cells lines are used to grow vaccine viruses, the resultant vaccine does not contain these cells, fragments of these cells, or any DNA recognisable as human. During the manufacturing process, the foetal cells often burst when the vaccine virus grows, and the resulting vaccine virus is purified before being used in the final vaccine product.

In 2005, Pope Benedict XVI as head of the Catholic Church, released a statement in support of using vaccines derived from foetal cell lines, outlining that they “may be considered in order to avoid a serious risk not only for one’s own children but also, and perhaps more specifically, for the health conditions of the population as a whole – especially for pregnant women”. They may be “morally justified as an extrema ratio due to the necessity to provide for the good of one’s children and of the people who come in contact with the children” [refer to Moral reflections on vaccines prepared from cells derived from aborted human foetuses].

Resources

• Children’s Hospital of Philadelphia, Vaccine Education Centre: Vaccine Ingredients- fetal tissues
• Children’s Hospital of Philadelphia, Vaccine Education Centre: News & Views- Why were fetal cells used to make certain vaccines?
• Johns Hopkins Bloomberg School of Public Health, Institute for Vaccine Safety: Religion and Vaccines
• Pontifical Academy for Life: Note on Italian vaccine issue, 2017
• NCIRS: Vaccine components fact sheet
• Australian Government Department of Health and Ageing: Myths and Realities, responding to arguments against vaccination (5th edition 2013)