PUBLISHED research linking CSL’s influenza vaccine to high rates of fever in children was omitted from the product information for its 2010 Fluvax product, which caused serious adverse reactions in children.

The product information (PI) included data from the 2005 flu season showing that after receiving Fluvax, fever was experienced by 22.5% of children aged from 6 months to less than 3 years and 15.6% of children aged from 3 years to less than 9 years.

However, the PI omitted data from the 2006 season which showed that the rate of fever had increased considerably — to 39.5% in the younger age group and 27% in the older group. Of the 272 children who received the 2006 vaccine, one child in the older group experienced a febrile convulsion.

This research was conducted in Australia in the 2005 and 2006 flu seasons and was published online by a peer-reviewed journal in October 2009 before publication of the PI, although CSL did not give this data to the TGA before 2010. (1)

Professor Peter Collignon, professor of infectious diseases at the Australian National University, said the fact this data wasn’t included in the PI was “a real worry”.

“It strikes me that the product information ought to reflect the latest data, particularly when the data show an increase in side effects compared with previous studies”, Professor Collignon said in an article published rapid online by the MJA today. (2)

Professor Collignon said that the Therapeutic Goods Administration (TGA) should routinely require that the most up-to-date research was included in PIs.

CSL did not include the published data in the PI because the increase in fevers seen in 2006 was not deemed “clinically substantial” at the time.

“The fevers did go up in total, but they were mostly mild or moderate; there wasn’t a significant increase in severe fever”, said Dr Darryl Maher, medical and research director at CSL Biotherapies.

However, Professor Collignon said it was important to weigh the risks of the vaccine with the risks of influenza itself.

“By my calculations, if more than one child in 1000 has a febrile seizure, the vaccine is doing more harm than good”.

In 2010, Fluvax was found to be causally linked to a significantly increased rate of fevers and febrile convulsions among Australian children. One published estimate put the rate of paediatric febrile convulsions at 3.3 per 1000 doses, or more than 200 times the rate in the only other published population-based estimate. (3)

After Fluvax was linked to the febrile seizures in 2010, CSL re-examined its clinical research including the data from 2006 and now acknowledges that, in retrospect, there were some warning signs.

“In retrospect, having had the events of last year and the results of [subsequent research] when you look back on that data you think, well, maybe that was telling us something”, Dr Maher said.

CSL is planning to add the data from the 2006 season to next year’s PI. However, it was not included in the PI for 2011 Fluvax, although this PI did include a warning that the product was not indicated for children under 5 years.

Investigations are ongoing as to the cause of the febrile reactions seen in 2010.

“Perhaps the way we make the vaccine is more inclined to cause fever in children, and maybe last year’s strain combination then tipped them over the edge and led to severe fevers and febrile convulsions. That’s our current thinking”, Dr Maher said.

– Sophie McNamara

1. Influenza and other respiratory viruses 2009; 3: 315-325

2. MJA 2011; 17 October (online)
3. BMJ Open 2011; 1: e000016

Posted 17 October 2011

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5 thoughts on “Fluvax PI omitted fever data

  1. Michael PEM says:

    I agree with Sue. Influenza is a nasty infection in many children and has led to deaths and severe morbidity as well, as well as in the adult and adolescent populations. Pointing to a single case where there were atypical circumstances and saying that all children should be denied protection because of that outcome is not good science. Yes, Saba’s case was bad – it will cause her and her family a lot of sadness over the years. However, simple febrile convulsions are very common in paediatric emergency departments (I would estimate closer to at least a daily event during the height of viral/flu season) and are not dangerous (although they are frightening if inadequate explanations are given). Allowing more children to get the native infection is likely to result in much worse outcomes

  2. Sue Ieraci says:

    Shotinfo – you may have misunderstood the terminology. I used the term “simple febrile convulsion”, which has a specific clinical definition (in terms of duration, age range, etc). THAT is a specific benign entity, and is by far the most common type of febrile convulsion in children – generally following a febrile illness from an infectious agent. Of course, some unfortunate children have prolonged febrile seizures, with lasting neurological effects (ie, no longer defined as “simple febrile convulsion”). These are rare, but occur much more commonly in the setting of an infectious disease rather than an immunisation.
    You say “I do believe we should not be saying that febrile seizures are common”. But the fact is, they ARE common. Emergency departments and general practitioners see them on a daily or weekly basis – especially during the winter peak in infectious diseases.
    As far as the importance of the vaccine goes, a recent review of the topic by Petrovski and Sajkov, from Adelaide, made the following points about the importance of preventing influenza in young children: “While the elderly suffer the vast burden of seasonal influenza morbidity and mortality, there is also an increased disease burden in very young children, a population in which approximately 1–5% of influenza deaths occur.
    “One reason for the increased disease burden of influenza in young children is that the frequency of influenza infection is much higher in children than in any other age group. Children, as a group, are more susceptible to infection as many are immunologically naive to influenza viruses. This, combined with their notoriously poor hygiene and their concentration in institutions such as daycare and schools, makes them an ideal vector for viral transmission.”
    And a Lancet paper addresses your point about efficacy:
    (Lancet Infectious Diseases Vol 11 Issue 1, Heinonen et all, Nov 2010) it looked at 631 vaccinated and unvaccinated children, including 268 aged under 4 years, and found that “Trivalent inactivated influenza vaccine was effective in preventing influenza in young children, including those younger than 2 years. “

  3. shotinfo says:

    Sue, you make two assumptions:

    1. That the flu vaccine will prevent influenza in vaccine recipients. The Cochrane Collaboration says that the evidence of that is pretty thin on the ground and in children under the age of two, the vaccine is no more effective than a placebo. So you have a lot of risk for an unknown or no benefit.
    2. You say that febrile seizures are benign by definition. Please try telling that to the family of Saba Button – the little girl in WA who was permanently injured by this vaccine after suffering febrile seizures. Febrile seizures are more likely to be benign than afebrile seizures (also known to follow vaccination), but there is a long history of permanent brain damage after no other symptoms than febrile seizures so I do believe that your statement is not correct.
    Lastly, do we have any figures on the incidence of febrile seizures before the introduction of childhood vaccines? Without access to any information on the background incidence, I do believe we should not be saying that febrile seizures are common. They may be common after vaccination – but they may not be common in normal circumstances.

  4. Sue Ieraci says:

    Peter Collignon says:
    “if more than one child in 1000 has a febrile seizure, the vaccine is doing more harm than good”. This point is rarely mentioned in the vaccine-safety discussion – what is the net effect of febrile seizures saved vs febrile seizures caused?

    Quite apart from the need for honesty and transparency (which can’t be disputed), we also need an honest and transparent debate about what “vaccine side-effects” actually consist of. Yes, vaccines can cause fever, which can cause febrile seizures. But vaccines are also preventing infectious diseases that can cause much more than fever and febrile seizures. A simple febrile convulsion, although frightening, is a relatively common and relatively benign phenomenon, and has no lasting effects (by definition). On the other hand, measles commonly causes much more morbidity than a simple febrile convulsion. Require transparency, certainly, but the same principle needs to apply throughout the discussion.

  5. shotinfo says:

    To me, the biggest problem isn’t that CSL omitted (is this is euphemism for covered up?) data on known risks of high fever and seizures from a vaccine targeting children, it is that the TGA allowed this to happen. The TGA is a true toothless tiger whose apparent role is to guard the henhouse but who, in actuality, makes a living by ensuring that the foxes are well fed.

    We need a drug regulator that is funded by the government to ensure that drugs and vaccines are safe and effective. The only way for them to do this is to test them themselves and to NOT be funded by the very companies they are meant to oversee.

    Cost recovery must end now. The TGA must either do its job or another, better agency should take its place. There is no other way.

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