Australia suspends seasonal flu vaccination of young children

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.

References

1.    Sweet M. Australia suspends seasonal flu
vaccination of young children. BMJ. 2010 May
4;340(may04_2):c2419.  http://www.bmj.com/cgi/content/extract/340/may04_2/c2419


2.    Reed J. Flu reactions cause still unclear
[Internet]. 6minutes. 2010 Apr 27 [cited 2010 May 5];Available from: http://www.6minutes.com.au/articles/z1/view.asp?id=516097


3.    Bita N. Suspended flu jab caused fits in 67 kids
[Internet]. The Australian. 2010 Apr 30 [cited 2010 May 5];Available
from: http://www.theaustralian.com.au/news/health-science/suspended-flu-jab-caused-fits-in-67-kids/story-e6frg8y6-1225860374357


4.    Simmons A. Flu jab scare sparks call for
surveillance system [Internet]. 2010 23T16:38:00+10:00 4 [cited 2010
Apr 24];Available from: http://www.abc.net.au/news/stories/2010/04/23/2881522.htm


5.    U.S. National Vaccine Advisory Committee. Report
on 2009 H1N1 Vaccine Safety Risk Assessment [Internet]. 2010 Apr 28
[cited 2010 Apr 30];Available from: http://www.hhs.gov/nvpo/nvac/reports/vsrawg_report_apr2010.html


6.    CSL. Fluvax Inactivated Influenza Vaccine (Split
Virion). Product information [Internet]. 2009 Nov [cited 2010 May
5];Available from: http://www.csl.com.au/s1/cs/auhq/1217017237558/Web_Product_C/1196562642777/ProductDetail.htm


7.    Nolan T, McVernon J, Skeljo M, Richmond P, Wadia
U, Lambert S, et al. Immunogenicity of a Monovalent 2009 Influenza
A(H1N1) Vaccine in Infants and Children: A Randomized Trial. JAMA. 2010
Jan 6;303(1):37-46. http://jama.ama-assn.org/cgi/content/full/303/1/37


8.    Nolan T, McVernon J, Skeljo M, Richmond P, Wadia
U, Lambert S, et al. Immunogenicity of a Monovalent 2009 Influenza
A(H1N1) Vaccine in Infants and Children: A Randomized Trial. JAMA. 2010
Jan 6;303(1):Supplementary online content.  http://jama.ama-assn.org/cgi/content/full/2009.1911/DC1


9.    World Health Organization. Safety of pandemic
vaccines [Internet]. 2009 Aug 6 [cited 2009 Aug 14];Available from: http://www.who.int/csr/disease/swineflu/notes/h1n1_safety_vaccines_20090805/en/index.html


10.    Jefferson T, Rivetti A, Harnden A, Di Pietrantonj
C, Demicheli V. Vaccines for preventing influenza in healthy children.
Cochrane Database Syst Rev. 2008;(2):CD004879. http://www3.interscience.wiley.com/homepages/106568753/CD004879_standard.pdf


11.    Jefferson T, Smith S, Demicheli V, Harnden A,
Rivetti A. Safety of influenza vaccines in children. Lancet. 2005 Sep
3;366(9488):803-804.


12.    Sebelius K. Pandemic Influenza
Vaccines--Amendment [Internet]. 2009 Jun 25;Available from: http://edocket.access.gpo.gov/2009/pdf/E9-14948.pdf


13.    Lakhani N. Swine flu in Britain: The guessing
game [Internet]. 2009 Jul 19 [cited 2009 Aug 11];Available from: http://www.independent.co.uk/life-style/health-and-families/health-news/swine-flu-in-britain-the-guessing-game-1752302.html


14.    Legal immunity set for swine flu vaccine makers -
Swine flu [Internet].  [cited 2010 May 6];Available from: http://www.msnbc.msn.com/id/31971355/
Other vaccine contracts between the French, German, and Italian
government and manufacturers are available at http://attentiallebufale.it/uncategorized/contract-fishing/


15.    New South Wales public health network.
Progression and impact of the first winter wave of the 2009 pandemic
H1N1 influenza in New South Wales, Australia. Euro Surveill [Internet].
2009 Oct 22 [cited 2010 May 5];Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19365


16.    Rosenthal S, Chen R. The reporting sensitivities
of two passive surveillance systems for vaccine adverse events. Am J
Public Health. 1995 Dec 1;85(12):1706-1709. http://ajph.aphapublications.org/cgi/reprint/85/12/1706


17.    Jefferson T, Di Pietrantonj C, Debalini MG,
Rivetti A, Demicheli V. Relation of study quality, concordance, take
home message, funding, and impact in studies of influenza vaccines:
systematic review. BMJ. 2009;338:b354. http://www.bmj.com/cgi/content/full/338/feb12_2/b354

Competing interests:
TJ is author of the relevant Cochrane reviews.