VACCINE

BMJ • May 2010
Australia suspends seasonal flu vaccination of young children
Adverse events
following influenza vaccination in Australia—
should we be surprised?
There have been large numbers of major adverse reactions to this year’s seasonal
influenza vaccine in Australia, and the vaccine has been suspended for use in children
aged five and under [1,2]. These reactions have occurred across the country
and involved multiple batches of vaccine [2]. In the state of Western Australia
where the problem was first detected, reports suggest that of the 20,000 to 30,000
children vaccinated, more than 250 had adverse reactions and 55 had febrile convulsions
before vaccination was suspended in young children [2]. Assuming all
convulsions were in children, about one child in every 500 vaccinated had a febrile
convulsion. Across Australia, media accounts indicate that more than 400 adverse
reactions [3] including 77 cases of febrile convulsion [1] have been reported by
regulators. While attention remains focused on reactions in very young children,
reports suggest only one-third of the reactions may have occurred in children under
five [4].
Although this situation has triggered considerable controversy in Australia, the
story has attracted little to no media attention in the US and Europe. Similarly,
the media has paid little attention to a US H1N1 federal vaccine safety advisory
committee which recently reported detecting signals for Guillain-Barre syndrome
(GBS), Bell’s palsy, and thrombocytopenia in the monovalent H1N1 (swine flu)
vaccine [5]. The same monovalent H1N1 antigen component under review in the
US is scheduled to be added to the US trivalent seasonal vaccine and is contained
in the Australian trivalent seasonal vaccine and will be given to children, pregnant
women and adults [6].
Data from a previous Australian study of H1N1 vaccine show that a large percentage
of children developed fevers following vaccination — in children less than 3
years, between three and six in every ten vaccinated, depending on dose [7,8]. The
data also show a dose response effect — the larger the vaccine dose, the more severe
the harms. There was also an age relationship: children under the age of three
developed fevers at more than twice the rate of older children [7,8]. The study was
however underpowered to detect febrile convulsions at the current rates in Australia,
with only 162 children below the age of three. The size problem was further
aggravated by stratification by age group and antigen dose.
Presumably the vaccine manufacturer CSL, which sponsored the trial, and Australia’s
regulatory body, the Therapeutic Goods Administration (TGA), which used
this data in approving the vaccine for children, were aware of these important findings.
But authors of the study published earlier this year did not discuss the high
incidence of fever associated with vaccination [7]; data were instead only reported
in online-only supplementary tables [8].
Overall, the percentages of children under three who developed a fever after vaccination
appear very high; thirty five per cent with the 15 ug dose and 62% after a 30
ug dose [7,8]. Of those that received a 7.5 ug dose in the seasonal influenza vaccine,
23% develop a fever of >38 degrees Celsius [6].
The large number of children suffering harms — and subsequent suspension of the
vaccine — challenges the assumption that regulators are ensuring the safety and
efficacy of all marketed therapeutics. Should we be surprised that these problems
have occurred with influenza vaccine, a vaccine used for over 60 years, said to have
“an established record of safety in all age groups”? [9]
There are actually relatively little data on the effects of vaccinating young children
against influenza [10]. Some manufacturers have even withheld data from public
scrutiny amidst general indifference [10,11]. Evidence from all comparative influenza
vaccine studies shows that harms, when they are investigated, are not reported
consistently and systematically [10,11].
As pandemic vaccines are provided to governments and not individuals and manufacturers
are indemnified for damages caused to users [12-14], there seem to be few
incentives for investigation of harms.
Last winter, the likelihood that a child without risk factors would die from swine
flu was less than one in a million [15]. When such a high proportion of children
develop moderate to severe febrile reactions to the influenza vaccine, it’s likely that
more harm than good will occur by vaccinating the entire population.
If such a large proportion of children develop high fevers, it is also likely that a
substantial number will develop febrile convulsions as a result of vaccination. It
is thus surprising the vaccine was approved for this age group. It is also surprising
that more explicit warnings about the high risk of adverse reactions were not given
to parents when their children were being vaccinated. Passive surveillance (as in
Australia and elsewhere) is a relatively weak mechanism to detect and evaluate
post-vaccination adverse events [16].
Unlike most drugs, vaccines are used on a population basis triggered by public
health policy. As such, evidence of their safety and efficacy needs to be extraordinarily
rigorous and evaluation methods and data should be open to independent
scrutiny. We need much better and larger studies on both safety and efficacy before
we roll out influenza vaccine programs to all populations, especially to children
who appear to have much higher rates of adverse reactions. Finally, decisions to
use a vaccine in a population must consider its safety profile, but principally its
effectiveness. There is poor evidence on how well influenza vaccines prevent any
influenza complications in children [10] and other age groups. There is good evidence
that influenza vaccines study reports cherry pick results and achieve spurious
notoriety [17]. Exposing human beings to uncertain effects is a risky business.
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“The large number of children
suffering harms — and subsequent
suspension of the vaccine —
challenges the assumption that
regulators are ensuring the
safety and efficacy of all marketed
therapeutics. Should we be
surprised that these problems have
occurred with influenza vaccine, a
vaccine used for over 60 years, said
to have “an established record of
safety in all age groups”?
There are actually relatively little
data on the effects of vaccinating
young children against influenza.
Some manufacturers have even
withheld data from public scrutiny
amidst general indifference.
Evidence from all comparative
influenza vaccine studies shows
that harms, when they are
investigated, are not reported
consistently and systematically.
As pandemic vaccines are provided
to governments and not individuals
and manufacturers are indemnified
for damages caused to users, there
seem to be few incentives for
investigation of harms.”