Australia suspends seasonal flu vaccination of young childrenBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2419 (Published 04 May 2010) Cite this as: BMJ 2010;340:c2419
All rapid responses
Influenza vaccines for children: the benefits far outweigh the risks
Collignon, Doshi and Jefferson have reignited the debate about
influenza vaccines in children in the BMJ's Rapid Reponses on 11 March
2011, following the preliminary finding, reported at the most recent US
Advisory Committee on Immunization Practice meeting, of a higher than
expected rate of febrile convulsions when conjugate pneumococcal vaccine
is given concomitantly with influenza vaccine
-vsd.pdf). However, in order to evaluate the risks and benefits of
influenza vaccination for young children, the situation needs to be
examined more rigorously and without selective presentation of data.
There is no doubt that the seasonal influenza vaccine manufactured by
CSL Limited (Australia) for distribution in 2010 caused a high rate of
febrile convulsions in young children (1). This vaccine is no longer
recommended for children under 5 years of age in any country where CSL
vaccines are licenced. However, no other manufacturer's seasonal influenza
vaccine was associated with an increased rate of febrile convulsions and
previous studies have not found any such association in Australia or
elsewhere (1). To generalise from a very specific issue is unjustified.
Direct comparison of risk and benefit for influenza vaccines in
children aged less than 5 years, who have the highest incidence of
convulsions in association with fever from any cause including influenza
infection and occasionally vaccines, is not easy. A comparison of the
number of children hospitalised for a febrile convulsion following receipt
of influenza vaccine with the number whose hospitalisation was prevented
by the vaccine in the experience of Western Australia showed that benefit
outweighed risk of hospitalisation for a febrile convulsion by 20:1 to
120:1, depending on the relative severity of the influenza season between
2001 and 2005 (H. Kelly, unpublished data). This was not the case in 2010
in the context of a highly pyrogenic vaccine (2). However, this simple
comparison is likely to underestimate the benefit of influenza vaccine,
because it does not account for the longer period of time that a child
with influenza is hospitalised compared with a child with a simple febrile
convulsion, or for the generally more serious consequences associated with
hospitalisation due to influenza. It also ignores deaths. Children die
from influenza. In the four years from 2003 to 2006, ten children under 5
years old were identified as having influenza-related deaths in Australia,
which has a population of less than 22 million and about 1.3 million
children <5 years old (3,4). No deaths were recorded from febrile
There is accumulating evidence that seasonal influenza immunisation is effective in children less than 2-3 years old (5-7). There is also good quality
evidence that routine immunisation of schoolchildren protects adults (8),
especially the elderly (9), through herd immunity. The overall safety
record of trivalent inactivated influenza vaccine in young children is
excellent (10). The challenge with respect to use of the inactivated
influenza vaccine in young children is not demonstrating safety and
efficacy (11), but the practicalities of delivering two doses of the
vaccine in the first year, followed by annual vaccination.
David Isaacs (email@example.com), Robert Booy (firstname.lastname@example.org),
Kristine Macartney (email@example.com), Peter McIntyre
(firstname.lastname@example.org), Children's Hospital at Westmead, Westmead, NSW, 2145,
Heath Kelly (Heath.Kelly@mh.org.au) Victorian Infectious Diseases
Reference Laboratory (VIDRL), 10 Wreckyn St, Nth Melbourne, Victoria,
1. Australian Government Department of Health and Ageing. Investigation
into febrile reactions in young children following 2010 seasonal trivalent
influenza vaccination. 2nd July 2010. Link:
2. Kelly H, Carcione D, Dowse G, Effler P. Quantifying benefits and risks
of vaccinating Australian children aged six months to four years with
trivalent inactivated seasonal influenza vaccine in 2010. Euro Surveill.
2010; 15: 19661. Available from:
3. Brotherton J, Wang H, Schaffer A, et al. Vaccine preventable diseases
and vaccination coverage in Australia, 2003 to 2005. Commun Dis Intell
2007; 31 Suppl: S1-S152.
4. Chiu C, Dey A, Wang H, et al. Vaccine preventable diseases in
Australia, 2006 to 2007. Commun Dis Intell 2010; 34 Suppl: S1-S167.
5. Heinonen S, Silve nnoinen H, Lehtinen P, Vainionp?? R, Ziegler T,
Heikkinen T. Effectiveness of inactivated influenza vaccine in children
aged 9 months to 3 years: an observational cohort study. The Lancet
Infectious Diseases 2011; 11: 23-9.
6. Katayose M, Hosoya M, Haneda T, et al. The effectiveness of trivalent
inactivated influenza vaccine in children over six consecutive influenza
seasons. Vaccine 2011; 29: 1844-9.
7. Sakkou Z, Stripeli F, Papadopoulos NG, et al. Impact of influenza
infection on children's hospital admissions during two seasons in Athens,
Greece. Vaccine 2011; 29: 1167-72.
8. Loeb M, Russell ML, Moss L. Effect of Influenza Vaccination of Children
on Infection Rates in Hutterite Communities. JAMA 2010; 303: 943-50.
9. Cohen SA, Chui KK, Naumova EN. Influenza vaccination in young children
reduces influenza-associated hospitalizations in older adults, 2002-2006.
J Am Geriatr Soc 2011; 59: 327-32.
10. Hambidge SJ, Glanz JM, France EK, et al. Safety of trivalent
inactivated influenza vaccine in children 6 to 23 months old. JAMA 2006;
11. Centers for Disease Control and Prevention (CDC). Prevention and
control of influenza: recommendations of the Advisory Committee on
Immunization Practices, 2007. MMWR - Morbidity & Mortality Weekly
Report 2007; 56(RR-6): 1-55.
Competing interests: No competing interests
"Influenza vaccines in children: more harm than good?"
National authorities worldwide promote influenza vaccines, arguing
they are not just effective, but extremely safe. The US NIAID director
claimed that "the track record for serious adverse events is very good.
It's very, very, very rare that you ever see anything that's associated
with the vaccine that's a serious event". (1)
There is now abundant evidence that such optimism is misguided. In
Australia last year, one febrile convulsion occurred for every 100 to 200
young children vaccinated with CSL's influenza vaccine (2,3,4). Now in
the US there have been similar concerns. A recent analysis of the
American experience reported a rate of 60 seizures per 100,000 influenza
vaccinations when given together with conjugated pneumococcal vaccine (5).
However this is likely to under-estimate the true rate. One post-marketing
vaccine safety study showed reports of febrile seizures admitted to
hospital, was 5 times lower with passive surveillance (6).
US authorities describe febrile convulsions as "very frightening for
parents," but "fairly common" and self-limiting (7). Yet febrile
convulsions are the cause of emergency room visits, and in Australia's
recent experience, 38% of children with febrile convulsions following
vaccination (19 of 56) were admitted to hospital (4).
Vaccine policies must ensure they are doing more good than harm.
Vaccine must cause far fewer serious adverse events compared to what the
disease would have caused in the vaccine's absence. Evidence suggests
this is not the case with influenza. In Australia in 2009, during winter
when young children (0-4 years) were first hit with the new H1N1 strain,
the admission rate for influenza was 57 per 100,000 (8). In the US, CDC
says that influenza results in hospitalization for approximately 20 per
100,000 children aged 2 to 5 years (9), but vaccine-induced febrile
convulsions resulting in hospitalization in US young children, likely
occurred at a rate of 114 per 100,000 children vaccinated . According to
the FDA, a "serious adverse event" is defined as hospitalization that
results from a vaccine adverse event (10). Thus vaccinating young children
without risk factors likely caused more serious adverse events than
disease from the new "pandemic" itself.
There is poor safety data available for other serious adverse events
that might occur in young children in addition to febrile seizures (11).
Evidence from systematic reviews show evidence of data suppression of
vaccine-associated harms to small children by some pharmaceutical
companies (12). Other reports suggest that influenza vaccines put children
at higher risk of future influenza infections compared to acquiring
natural infection (original antigenic sin) (13). In older children,
unexpected adverse events such as narcolepsy have been reported from at
least 12 countries (14). In Canada previous immunisation with seasonal
influenza vaccine doubled your risk of being infected with "swine flu"
In 2005, when a new study demonstrated that influenza vaccines were
not saving elderly lives (16), many argued that this underscored the
importance of vaccinating more children (17). Yet we have no evidence
demonstrating that children are benefiting from this strategy but do have
evidence that these vaccines are hospitalizing children. The recent H1N1
"pandemic" and our immunisation response show that in children we likely
caused more harm than good. Public health authorities should not continue
to recommend (as in the US), that all children receive routine influenza
vaccine until we have much better safety and efficacy data.
1. How Safe is the Flu Vaccine? 2009 [cited 2010 May 8]. Available
2. Collignon P, Doshi P, Jefferson T. Adverse events following
influenza vaccination in Australia--should we be surprised? (7 May 2010)
3. TGA. Investigation into febrile reactions in young children
following 2010 seasonal trivalent influenza vaccination. Updated 24
September 2010. http://bit.ly/e3bPbp
4. Kelly H, Carcione D, Dowse G, Effler P. Quantifying benefits and
risks of vaccinating Australian children aged six months to four years
with trivalent inactivated seasonal influenza vaccine in 2010. Euro
5. Small Seizure Risk With Flu, Pneumococcal Vaccines CDC Says
Getting the Vaccines Together Raises Risk of Febrile Seizure in Kids By
Daniel J. DeNoon WebMD Health News.
6. Farrington P, Pugh S, Colville A, et al. A new method for active
surveillance of adverse events from diphtheria/tetanus/pertussis and
measles/mumps/rubella vaccines. Lancet 1995;345:567-9.
7. CDC. Febrile Seizures Following Childhood Vaccinations, Including
Influenza Vaccination. (October 12, 2010) Available online:
8. New South Wales public health network. Progression and impact of
the first winter wave of the 2009 pandemic H1N1 influenza in New
SouthWales, Australia. Euro Surveill. 2009;14(42):pii=19365.
9. Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, Singleton JA,
et al. Prevention and control of influenza with vaccines: recommendations
of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR
Recomm Rep. 2010 Aug 6;59(RR-8):1-62.
10. FDA definition of serious adverse events.
11. Jefferson T, Rivetti A, Harnden AR, Di Pietrantonj C, Demicheli
V. Vaccines for preventing influenza in healthy children. Cochrane
Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004879. DOI:
12. Jefferson T, Smith S, Demicheli V, Harnden A, Rivetti A. Safety
of influenza vaccines in children. Lancet. 2005 Sep 3;366(9488):803-804.
13. Morens DM, Burke DS, Halstead SB. The wages of original antigenic
sin. Emerg Infect Dis. 2010 June.
14. Increased risk of narcolepsy observed among children and
adolescents vaccinated with PandemrixR.
15. Skowronski DM, De Serres G, Crowcroft NS, Janjua NZ et al.
Canadian SAVOIR Team. Association between the 2008-09 seasonal influenza
vaccine and pandemic H1N1 illness during Spring-Summer 2009: four
observational studies from Canada. PLoS Med. 2010 Apr 6;7(4):e1000258.
16. Simonsen L, Reichert TA, Viboud C, Blackwelder WC, Taylor RJ,
Miller MA. Impact of Influenza Vaccination on Seasonal Mortality in the US
Elderly Population. Arch Intern Med. 2005 Feb 14;165(3):265-272.
17. Cohen J. INFLUENZA: Study Questions the Benefits of Vaccinating
the Elderly. Science. 2005 2;307(5712):1026-1026.
Infectious Diseases Physician and Microbiologist
Director Infectious Diseases Unit and Microbiology Department, The
Professor, School of Clinical Medicine, Australian National University.
PO Box 11, Woden, ACT. 2607. Australia
Program in History, Anthropology, Science, Technology and Society,
Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
Coordinator, Cochrane Vaccines Field, Rome, Italy.
Competing interests: TJ is an author of the relevant Cochrane reviews.All others no competing interests
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 . 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 . 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  including 77 cases of febrile convulsion  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 .
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
. 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 .
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
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 ; data were instead only reported in
online-only supplementary tables .
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 .
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 [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 . 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 .
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  and other age groups. There is good evidence that
influenza vaccines study reports cherry pick results and achieve
spurious notoriety . Exposing human beings to uncertain effects is
a risky business.
1. Sweet M. Australia suspends seasonal flu
vaccination of young children. BMJ. 2010 May
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
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[Internet]. The Australian. 2010 Apr 30 [cited 2010 May 5];Available
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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
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
TJ is author of the relevant Cochrane reviews.
Competing interests: No competing interests