H1N1 immunisation: too much too soon? by Peter Collignon, Infectious Diseases Physician and Microbiologist

[Guest guest]

Editorial

H1N1 immunisation: too much too soon?

Peter Collignon, Infectious Diseases Physician and Microbiologist,, Infectious Diseases Unit and Microbiology Department, The

Canberra Hospital, and Professor, School of Clinical Medicine, Australian

National University, Canberra

Key words: adverse effects, influenza vaccines, vaccination.

 

 

http://www.australianprescriber.com/magazine/33/2/30/1/

(Aust Prescr 2010;33:30-1)

In April 2009, a new influenza strain − H1N1 'swine flu' − was

identified in Mexico with an apparent high case fatality rate (about 5%).

As H1N1 spread rapidly throughout the world it caused not only a

'pandemic' but also widespread fear. However, overall, swine flu has been

associated with fewer deaths (case fatality rate < 0.01%) than

seasonal influenza (case fatality rate < 0.1%

approx.),

1 and is of low virulence. While younger people were

disproportionately infected by swine flu, it was people aged 50–60 years

who had more frequent serious illness in terms of admissions to intensive

care units and

deaths.

2–4

In the 2009 Australian winter, swine flu's associated mortality rate was

0.9 per 100 000 people. In those under 40 years with no risk factors, the

mortality rate was less than one per

million.

3 While there were some differences (for example pregnant women), the

overall effects of this virus as judged by absenteeism, hospitalisations

and deaths were similar to those of previous seasonal influenza

strains.

2–4

While swine flu is a 'new' virus, it is an H1N1 virus, strains of which

have been circulating since 1918. Not surprisingly, many people have

pre-existing immunity. Most people over 65 years appear to be immune, as

reflected by their low infection rates. In an Australian H1N1 vaccine

trial of adults (aged 18–65 years), 27% had protective antibody

concentrations and 62% had detectable pre-existing

antibodies.

5 Most infections in the 2009 winter occurred in children and younger

adults.

2–4 It is likely therefore that more than 50% of the Australian

population are already immune because of pre-existing immunity or recent

infection. In any mass vaccination campaign, those who are already immune

are unlikely to get additional benefits from the vaccine, but remain at

risk of adverse effects.

The timing of a mass vaccination program is important. In Australia, our

mass vaccination program for this virus started in spring 2009. However,

it was very unlikely that the swine flu virus would circulate widely in

Australia during the summer. The composition of a trivalent vaccine for

next winter's seasonal influenza will include a swine flu component.

People already vaccinated against swine flu who need protection for

seasonal influenza will still need re-vaccination in autumn with the

trivalent vaccine as we cannot necessarily predict which influenza

strains will be circulating in winter 2010.

The use of multidose vials in the vaccination program was a needless

additional risk. In the past, many infections, such as Staphylococcus

aureus, hepatitis B and HIV, have been caused by vaccination programs

using multidose

vials.

2 Even a very low individual risk can translate into hundreds of

people with cross-infections when multidose vials are used in large

populations. Over eight million doses of trivalent seasonal influenza

vaccine are given per year in Australia using single-use preloaded

syringes. It is difficult to see why this could not have been done for

the swine flu vaccine. Also with multidose vials, large amounts of

vaccine may be wasted. The advantages of multidose vaccines are small

monetary savings in manufacture and the potential for a more rapid

roll-out of a vaccine. However, current technology allows single-dose

preloaded syringes to be rapidly manufactured.

We need to learn lessons from the past. In the USA in October 1976 there

was a mass immunisation campaign for H1N1 swine flu. Unexpectedly,

Guillain-Barré syndrome occurred at a rate of about 1 per 100 000

vaccine recipients. The expected swine flu epidemic did not eventuate.

Thus, the complications that occurred were not offset by any meaningful

benefits in the general population. It was only after 40 million people

had been vaccinated over two and a half months that the association of

these rare but serious adverse effects with the vaccine was accepted. The

program was stopped in December

1976.

6

In Australia, we do not have good postmarketing surveillance mechanisms

in place and mainly rely on voluntary reporting. This is unlikely to

accurately measure the percentage of people who get adverse effects or to

identify rare adverse effects in a timely fashion. A more effective way

might be to follow a large sample of vaccine recipients for, say, a

month. This could be done by practice nurses in a defined number of

general practices.

A problem with this vaccine and other influenza vaccines is that there

are relatively few well-designed, large randomised

studies.

5,

7 The efficacy of seasonal inactivated parenteral vaccines in

preventing influenza in healthy adults varies from 50% to

80%.

7 The often quoted efficacy for protection from all-cause mortality

with seasonal influenza vaccines is around 50%. However, those in

vaccinated groups frequently have fewer comorbidities than those in

non-vaccinated groups. A recent Californian study looked at over 100 000

deaths over nine

years

8 and showed that the decrease in all-cause mortality attributable to

seasonal influenza vaccine was 4.6%.

The reason these issues are important is that we do not have robust data

on which to make proper decisions on the cost-effectiveness of any mass

vaccine programs. In young people without risk factors, the rates of

death and complications last winter from swine flu were very low and are

similar to the risk of serious vaccine-associated adverse effects such as

Guillain-Barré syndrome and anaphylaxis. Around 50% of people who

received the H1N1 vaccine in the Australian trial had mild to moderate

systemic adverse effects and 1.7% had (solicited) systemic adverse

effects recorded as

severe.

5 In children, 20% had moderate to severe systemic adverse effects

after receiving a single 15 microgram dose of

vaccine.

9 It is very important that we make sure we do more good than harm

with any vaccine. Thus, we need a large cohort of people (tens of

thousands) followed prospectively so that we can accurately know what are

the percentages of people with adverse effects in the postmarketing

period. We also need a robust system to accurately detect the very rare

but serious adverse effects. Otherwise we risk repeating the mistakes

made in the 1976 USA swine flu vaccine

program.

6

The disproportionate fear generated by the swine flu virus has caused

many decisions to be made that in retrospect were inappropriate. We need

to learn from our experiences and more importantly ensure that

well-designed, large, prospective long-term studies are done so we can

answer basic questions on the true safety and efficacy of influenza

vaccines. This is not only in the elderly but also in groups proposed for

routine seasonal influenza campaigns such as children and pregnant women.

We need these types of data before embarking on further mass immunisation

programs, particularly if done during periods with likely low infection

rates (that is, summer) using multidose vials.

References

 

Flu.gov (U.S.).

Community strategy for pandemic influenza mitigation. 2007

Feb.

www.flu.gov/professional/community/mitigation.html

[cited 2010 Mar 12] Collignon P. Pandemic influenza: inappropriate fear

causes inappropriate responses. In healthcare we need good surveillance

data to make the best decisions [editorial]. Healthcare Infect

2009;14:77-9.

www.publish.csiro.au/view/journals/dsp_journal_fulltext.cfm?nid=241 & f=HI09021

[cited 2010 Mar 12] 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

2009;14:pii=19365.

www.eurosurveillance.org/View Article.aspx?ArticleId=19365

[cited 2010 Mar 12] Department of Health and Ageing. Australian influenza

surveillance summary report. No. 29, 2009, reporting period: 21 November

2009 – 27 November

2009.

www.healthemergency.gov.au/internet/healthemergency/publishing.nsf/Content/ozflu2009.htm/$File/ozflu-no29-2009.pdf

[cited 2010 Mar 12] Greenberg ME, Lai MH, Hartel GF, Wichems CH,

Gittleson C, Bennet J, et al. Response to a monovalent 2009 influenza A

(H1N1) vaccine. N Engl J Med 2009;361:2405-13.

 

http://content.nejm.org/cgi/reprint/361/25/2405.pdf [cited 2010 Mar

12] For supplementary appendix see

 

http://content.nejm.org/cgi/data/NEJMoa0907413/DC1/1

[cited 2010 Mar 12] Neustadt R, Fineberg H. The swine flu affair.

Decision-making on a slippery disease. Washington: U.S. Department of

Health, Education, and Welfare;

1978.

www.iom.edu/Global/News%20Announcements/~/media/

Files/swine%20flu%20affair%20electronic%20edition%20

200904web.ashx [cited 2010 Mar 12] Demicheli V, Di Pietrantonj C, Jefferson T, Rivetti

A, Rivetti D. Vaccines for preventing influenza in healthy adults.

Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.:

CD001269. DOI: 10.1002/14651858.CD001269.pub3.

 

www.cochrane.org/reviews/en/ab001269.html [cited 2010

Mar 12] Fireman B, Lee J, Lewis N, Bembom O, van der Laan M,

Baxter R. Influenza vaccination and mortality: differentiating vaccine

effects from bias. Am J Epidemiol 2009;170:650-6. Nolan T, Mc Vernon 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;303:37-46.

 

 

 

Sheri Nakken, R.N., MA, Hahnemannian

Homeopath

Vaccination Information & Choice Network, Washington State, USA

Vaccines -

 

http://vaccinationdangers.wordpress.com/ Homeopathy

 

http://homeopathycures.wordpress.com

Vaccine Dangers, Childhood Disease Classes & Homeopathy

Online/email courses - next classes start March 24, March 31, & April

1