This Cochrane review assesses the efficacy, effectiveness, and potential harms of influenza vaccines in healthy adults, finding a modest reduction in influenza symptoms but no significant impact on complications or transmission. While inactivated vaccines showed a vaccine efficacy of 73% when matching the vaccine content to circulating strains, adverse effects, including myalgia and rare disorders like Guillain-Barré syndrome, were reported. Overall, the review suggests that influenza vaccines may not significantly reduce the incidence of hospitalizations or pneumonia, highlighting the importance of considering the baseline risk of influenza in assessments of vaccine effectiveness.

1. Vaccines for preventing
influenza in healthy adults:
a Cochrane review
Clinical
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2. Clinical question
What are the effects (efficacy,
effectiveness and harm) of vaccines
against influenza in healthy adults?
Source: Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E.
Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic
Reviews 2010, Issue 7. Art. No.: CD001269. DOI: 10.1002/14651858.CD001269.pub4.
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3. Context
• Influenza is seen as an important threat to
health worldwide.
• Vaccines are the mainstay of its prevention.
• Each year, extensive vaccination campaigns
cover an increasing number of age groups.
• These campaigns are costly in money and
time.
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4. Methods
• This is an update of a Cochrane review, which was first published in 1999.
It was updated previously in 2004 and 2007.
• The specialised registers of the Cochrane Acute Respiratory Infections
(ARI) Group and the Cochrane Vaccines Field were used to identify trials.
The authors also searched the following bibliographic databases, most
recently in June 2010: Cochrane Central Register of Controlled Trials,
MEDLINE and EMBASE.
• A random effects model was used for the meta-analyses to calculate the
risk ratio (RR). The vaccine efficacy (VE) was estimated using the formula
VE =(1-RR)%. The risk difference (RD) and number needed to vaccinate
(NNV) were also estimated from the meta-analyses.
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5. PICO(S) to assess eligible studies
• Participants: Healthy individuals aged 16 to 65 years.
• Intervention: Live, attenuated or killed vaccines administered
by any route.
• Comparison: Placebo or standard care.
• Primary outcomes: Symptomatic influenza and influenza-like
illness (ILI) and systemic adverse effects.
• Secondary outcomes: Local adverse effects, time off work,
hospital admissions and transmission of influenza.
• Studies: Randomized and quasi-randomized trials for efficacy
or effectiveness, and comparative non-randomised studies for
harms.
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6. Description of eligible studies
• Fifty eligible reports were identified and included, an increase
of 2 over the previous version of the review.
• 40 trials (with 59 sub-studies, and more than 70,000 people)
reported data on effectiveness, efficacy and harms of
influenza vaccines. 20 (25 sub studies) of the trials tested
unlicensed aerosol vaccines, which had a very modest
performance and were not included in the meta-analyses.
• 8 comparative non-randomised studies investigated serious
harms. Two of these could not be included in the analysis.
• The main findings of the review are based on 26 clinical trials
of the effectiveness of inactivated vaccines and 10 studies of
the harms of the same vaccines.
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7. Results: inactivated influenza vaccines
• The risk ratio (RR) for influenza symptoms for vaccines in which the WHO
recommended content matched the circulating strain compared to no
vaccine or placebo was 0.27 (95% CI 0.16 to 0.46). This gives a vaccine
efficacy (VE) of 73% (95% CI 54% to 84%). The VE decreased to 44% (95% CI
23% to 59%) when matching of the vaccine was incomplete or not reported
(RR 0.56, 95% CI 0.41, 0.77).
• The risk difference (RD) in the case of complete matching of the vaccine is
–0.03 (95% CI –0.05 to –0.02). This corresponds to a number needed to
vaccinate (NNV) of 33 (ie an average of 33 healthy adults need to be
vaccinated for one fewer to develop influenza symptoms). With incomplete
matching or if matching was not reported, the RD was –0.01 (95% CI –0.03
to 0.00), with a NNV of 100.
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8. Efficacy of influenza vaccine in healthy adults
(vaccine content completely matching circulating strain)
Based on 8 clinical trials, 11,285 participants
100 healthy adults, vaccinated 100 healthy adults, not vaccinated
1 develops 4 develop
influenza influenza
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9. Efficacy of influenza vaccine in healthy adults
(vaccine content incompletely matching circulating strain or not reported)
Based on 6 clinical trials with 10,331 participants
100 healthy adults, vaccinated 100 healthy adults, not vaccinated
1 develops 2 develop
influenza influenza
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10. Results: systemic adverse effects
• Inactivated vaccines caused myalgia (RR 1.54, 95% CI 1.12 to 2.11, based on research
involving 2676 people).
• Several non-randomised studies assessed the association between inactivated
influenza vaccines and a variety of rare potential harms, such as cutaneous
melanoma, primary cardiac arrest, demyelinating diseases, pulmonary function,
oculo-respiratory syndrome, Guillan Barrè Syndrome and Bell’s Palsy, and the last
two of these appear to be related to inactivated vaccines.
• The occurrance of Guillan Barrè Syndrome was estimated as 1.6 to 10 extra cases
per million vaccinated (based on surveys of more than 21 million people).
• Bell’s Palsy was associated with administration of an intranasal inactivated virosomal
influenza vaccine (odds ratio 84.0, 95% CI 20.1 to 351.9) within 1 to 91 days after
vaccination. The product was withdrawn.
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11. Results: other outcomes
• Based on single studies, inactivated vaccines were not
effective in preventing pneumonia (RR 0.59, 95% CI
0.04 to 9.43) or hospitalisation (RR 0.37, 95% CI 0.12
to 1.12).
• They had a minimal effect on working days lost, with a
standardized mean difference of –0.21 (95% CI –0.36
to –0.05).
• No studies were identified which tested the effect on
interruption of transmission.
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12. Results: local harms
• Inactivated vaccines caused erythema (RR 4.01, 95% CI 1.91 to
8.41, based on 3388 observations) and tenderness or soreness
(RR 3.11, 95% CI 2.08 to 4.66, based on 6833 observations).
• There was no statistically significant effect on arm stiffness (RR
1.62, 95% CI 0.54 to 4.83, based on 50 observations) nor
induration (RR 2.24, 95% CI 0.48 to 10.59, based on 543
observations).
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13. Conclusions
• Influenza vaccines have a modest effect in reducing influenza
symptoms and working days lost among healthy adults. There
is no evidence that they affect complications (such as
pneumonia), or transmission.
• The dramatic difference between the apparent size of the
effect with the risk ratio (RR) and the risk difference (RD) is
because RR is a relative measure and RD is an absolute
measure taking account of the baseline risk of influenza.
• This baseline risk is relatively low. During the winter months
there will be 7 episodes of ILI among 100 adults, but fewer
than one of these is caused by influenza.
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14. How many influenza-like illnesses a year? How many of these are influenza?
Based on 274 studies of influenza vaccines and 28 epidemiological studies
from 1966 to 2007, with more than 3,000,000 participants
100 people
Influenza
A or B
7 people with flu episodes
(only 1 has influenza)
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15. Useful links
• Cochrane Journal Club discussion points
• Vaccines for preventing influenza in healthy
adults
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