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Analysis And Comment Public health

Influenza vaccination: policy versus evidence

BMJ 2006; 333 doi: https://doi.org/10.1136/bmj.38995.531701.80 (Published 26 October 2006) Cite this as: BMJ 2006;333:912

Rapid Response:

Influenza seasonal vaccination: is it enough?

Tom Jefferson’s paper (1) is a provoking and stimulating one. The
article should be read in parallel with a previous systematic review paper
on the same influenza vaccination subject by Jefferson and colleagues of
Cochrane Center, which appeared on “The Lancet” (2) one year before, and a
group of systematic review papers belonging to the Cochrane database (3-
6), to gain more insight on the original material upon which Jefferson
bases his considerations.

Jefferson states that for most of the declared objectives of the
vaccination campaign there is limited evidence of efficacy, and indeed
looking at Table 2 of the paper, it is difficult not to agree with him,
since significance is lacking very often and, when significant, the
Vaccine efficacy has a modest value for preventing Influenza-like Illness
(ILI) or Hospital admission for influenza and pneumonia. In view of this
fact, if one finds significance and a higher value for vaccine efficacy in
predicting death from all causes, one should be very cautious, especially
if a comparable efficacy for predicting death from more specific causes
like all respiratory diseases is missing. In this case, one should suspect
a possible selection bias, as Jefferson warns, since the vaccinated cohort
could be more healthy and wealthy than the non-vaccinated one. The
alternative possibility that frailer people are more likely to be
vaccinated is probable only in presence of high compliance of the
population. In a recent study, conducted in Seattle, USA, in 2006 (7) , on
a cohort of 72527 people 65 years old or more, followed for 8 years, the
relative risk of death for vaccinated persons, compared with non
vaccinated persons was 0.39 (95% CI 0.33-0.47) before influenza season,
0.56 (95% CI 0.52-0.61) during influenza season, and 0.74 (95% CI 0.67-
0.80) after influenza season, indicating preferential receipt of vaccine
by relatively healthy seniors.

In general, there are also reasons to doubt conventional estimates of the
mortality burden of influenza, as remarked previously by Doshi (8) on this
same journal.
Jefferson points out that one of the reasons for the gap between policy
and evidence is the potential confusion between influenza and ILI, in view
of the fact that very rarely these diseases are laboratory confirmed. The
“confusion” is not a small one, since it is well known that in non-
pandemic years, the forms of ILI due to agents different from influenza
are overall more frequent than true influenza during most of the year,
except for the peak period of the influenza epidemic, as documented in a
well-done monography distributed on-line by the Health Protection Agency
(HPA) of the U.K. (9). In fact, in the Communicable Disease Report on
influenza by the same Agency relative to the period October 2004 to May
2005 (10), virological surveillance on positive respiratory virus
specimens routinely reported to the Centre for Infection of HPA and of
National Health Service identified 1190 confirmed influenza A infections,
246 confirmed influenza B infections, and 5113 confirmed respiratory
syncytial virus (RSV) infections. Parainfluenza activity was not reported
in detail.

The presence of forms of illness that can be misunderstood as influenza,
but on which the vaccine has no effect, “dilutes” the efficacy of the
vaccination, as can be seen from Table 2 comparing the outcomes Influenza
and Influenza-like Illness, when they are both available. For instance
vaccine efficacy (VE) in a population of children 6 years or more is 69%
in preventing influenza, but only 28% in preventing ILI, while in a
population of healthy adults the same quantities are 67% and 22%.
From a Public Health point of view, the really important achievement would
be to prevent the complications of whatever form of ILI, and not only the
complications of influenza, and it is not demonstrated that in non-
pandemic years the complications due to other forms of ILI would
necessarily be milder than the complications of influenza, first of all
because this demonstration is a very difficult one, since in most cases it
is not possible to distinguish the illnesses, and also because several
recent papers pointed out the importance of the RSV virus as a threat to
Public Health (11-13).
The “confusion” caused by the presence of not-distinguishable illnesses
increases the perception of scarce efficacy of the vaccination among the
target population, thus potentially decreasing its compliance to the
recommendations of the campaign.

It would be wise to promote an information campaign aimed at increasing
the knowledge about influenza and the ILI in the general population. The
diffusion among General Practitioners of a pamphlet like the one mentioned
previously (9), and the involvement of the GPs in spreading the main
concepts and information about the different respiratory viruses
circulating normally during the different seasons of the year, could help
in decreasing the “confusion”.

It would also be useful to improve greatly the etiological assessment of
the viruses in the existing Surveillance systems. The aim should be to
detect not only the circulating strains of influenza, but also those of
the most common among the other ILI (RSV, Parainfluenza virus).
With the current situation of multiple agents, for some of which no
vaccines exist, and no perfect immunization on the horizon anyway, since a
limited overall efficacy of the vaccination should be expected, it would
be also wise to promote among the general population those old-forgotten
conventional preventive measures concerning personal hygiene and person-to
-person contacts, to prevent spread of ILI infections.

At the same time, stronger efforts, not only in identifying next year’s
influenza strains, but also in developing those much needed new vaccines
should be spent. After all, the Pharmaceutical industry should be able to
see its own interest in this enterprise, since a recent paper estimated
the economic burden of non-influenza-Related viral respiratory tract
infections in the United States in about 40 billions US$ (14).

The views expressed in this article reflect the personal opinions of
the author and not necessarily the views of the Istituto Superiore di
Sanità (Italian National Institute of Health).

References

1) Jefferson T. Influenza vaccination: policy versus evidence. BMJ 2006;
333: 912-915.

2) Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli
V. Efficacy and effectiveness of influenza vaccines in elderly people: a
systematic review. Lancet 2005;366: 1165-74.

3) Smith S, Demicheli V, Di Pietrantonj C, Harnden AR, Jefferson T,
Matheson NJ, et al. Vaccines for preventing influenza in healthy children.
Cochrane Database Syst Rev 2006;(1):CD004879.

4) Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for preventing
influenza in healthy adults. Cochrane Database Syst Rev 2004;(3):CD001269.

5) Thomas RE, Jefferson T, Demicheli V, Rivetti D. Influenza vaccination
for healthcare workers who work with the elderly. Cochrane Database Syst
Rev 2006;(3):CD005187.

6) Rivetti D, Demicheli V, Di Pietrantonj C, Jefferson TO, Thomas R.
Vaccines for preventing influenza in the elderly. Cochrane Database Syst
Rev 2006;(3):CD004876.

7) LA Jackson, ML Jackson, JC Nelson, et al. Evidence of bias in estimates
of influenza vaccine effectiveness in seniors. International Journal of
Epidemiology 2006;35:337–344.

8) Peter Doshi. Are US flu death figures more PR than science? BMJ
2005;331;1412-

9) Health Protection Agency. A Winter’s Tale: Coming to terms with winter
respiratory illnesses, HPA Reports, London, January 2005.

10) H Zhao, MK Cooke, CA Joseph et al. Surveillance of influenza and other
respiratory viruses in the United Kingdom: October 2004 to May 2005, CDR
Supplement, 2005.

11) NS Crowcroft, F Cutts, MC Zambon. Respiratory syncytial virus: an
underestimated cause of respiratory infection, with prospects for a
vaccine. Commun Dis Public Health 1999; 2: 234-41.

12) Hall CB. Respiratory syncytial virus and Parainfluenza virus. N Engl
J Med, Vol. 344, No. 25 June 21, 2001.

13) Dowell SF, Anderson LJ, Gary HE Jr et al. Respiratory syncytial virus
is an important cause of community-acquired lower respiratory infection
among hospitalized adults. J Infect Dis 1996; 174: 456-62.

14) Fendrick AM, Monto AS, Nightengale B, et al. The Economic Burden of
Non-Influenza-Related Viral Respiratory Tract Infection in the United
States. Arch Intern Med, v.163, Feb 24, 2003, p. 487.

Competing interests:
None declared

Competing interests: No competing interests

13 December 2006
Sergio Mariotti
Senior Researcher
Istituto Superiore di Sanità (National Institute of Health), 00161 Rome, Italy