Vaccines for Preventing Influenza in Healthy Individuals

Reduces the risk of influenza and influenza-like illness

Benefits in NNT

NNT of 71 for preventing influenza
29, 5
NNT of 29 for elderly and 5 for children
NNT of 29 for preventing influenza-like illness
42, 12
NNT of 42 for elderly and 12 for children
1.4% had lower risk of influenza
29, 5
3.4% and 19% lower risk of influenza in elderly and children
3.4% had lower risk of influenza-like illness
42, 12
2.5% and 8% lower risk of influenza-like illness in elderly and children

Harms in NNT

1 in 125 experienced fever after vaccination
0.8% more adults experienced fever after vaccination (compared to placebo)
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Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantoni C. Vaccines for preventing influenza in healthy adults. Cochrane Database of Systematic Reviews 2018, Issue 2. Art. No.: CD001269

Study Population: More than 80,000 healthy adults from 52 clinical trials aged 16 to 65 years, including pregnant women, over a single influenza season in North America, South America, and Europe who received vaccination between 1969 and 2009

Efficacy Endpoints

Incidence of influenza infection and influenza-like illness

Harm Endpoints

Adverse events including malaise, fever, arthralgia, rash, headache, and neurological harms


Influenza is an acute respiratory infection that imposes a heavy burden on society.1 The illness itself usually lasts a few days but the residual symptoms of cough and malaise can last for weeks. In addition, it can cause complications such as otitis media, pneumonia, secondary bacterial pneumonia, exacerbations of chronic respiratory disease, bronchiolitis, febrile seizures, Reye’s syndrome, and myocarditis.1 Vaccines have been developed in attempt to minimize the effects of influenza. However, given the yearly antigenic changes of the virus, a new vaccine has to be developed, produced, and administered to the population every year.2

The Cochrane review discussed here assesses the efficacy of vaccines in preventing influenza in healthy adults including pregnant women.2

A total of 52 clinical trials of over 80,000 healthy adults aged 16 to 65 years over a single influenza season in North America, South America, and Europe who received vaccination between 1969 and 2009 were included in this review. The results presented were from 25 studies comparing inactivated parenteral influenza vaccine against placebo control groups.2 Fifteen of the included trials were industry sponsored.2 The review concluded that healthy adults who received inactivated parenteral influenza vaccine rather than placebo were at lower risk of influenza infection; from 2.3% in the control group to 0.9% in the vaccinated group (number-needed-to-vaccinate [NNV]: 71; absolute risk difference [ARD] 1.4%; relative risk (RR): 0.41, 95% confidence interval [CI], 0.36-0.47, moderate certainty). People who received vaccination also experienced less influenza-like illness (ILI) (NNV: 29; RR: 0.84, 95% CI, 0.75-0.95). The rate of hospitalization and time out of work endpoints were not significantly different between vaccinated and un-vaccinated groups.2

There was an increase in risk of developing fever in the vaccinated group from 1.5% to 2.3% (RR: 1.55, 95% CI 1.26-1.91; ARD: 0.8%; Number-needed-to-harm [NNH]: 125).2 People also reported more nausea and vomiting after vaccination, however the risk of these adverse events was not statistically significant between the groups. No association was found between vaccination and Guillain-Barre syndrome or other neurological diseases.2 There was also no increased risk of abortion, congenital malformation, prematurity, or neonatal death in vaccinated pregnant women.2

Two other Cochrane systematic reviews assessed the benefits of flu vaccine in preventing influenza and ILI in healthy elderly3 and healthy children.4 These Cochrane reviews report a greater benefit from flu vaccine in these two vulnerable population. Among the healthy elderly, 29 people would need to be vaccinated to avoid one case of influenza (ARD: 3.4%; RR: 0.42, 95%CI, 0.27 to 0.66; low‐certainty evidence) and 42 people would need to be vaccinated to prevent one case of ILI (ARD: 2.5%; RR: 0.59, 95%CI, 0.47 to 0.73; moderate‐certainty evidence).3 The impact is even more pronounced in children (2 to 16 years of age) with an NNT of 5 for preventing influenza (ARD: 19%; RR:0.36, 95%CI, 0.28 to 0.48; high‐certainty evidence) and NNT of 12 for preventing ILI (ARD:8%, RR: 0.72, 95%CI, 0.65 to 0.79; moderate‐certainty evidence).4


A limitation of the presented data is the heterogenity of the included studies. The degree of benefit in reduction of ILI varied across different settings due to inconsistent definition and symptom classification for ILI.2 In most trials, influenza infection was confirmed by virus isolation from culture, a four-fold antibody increase in the acute or convalescent-phase or in post-vaccination phase.2

The vaccine strength varies year by year as the vaccine for one year is generally developed based on the flu strain from the previous year. Therefore, flu vaccine’s efficacy in preventing influenza may vary from one year to another.

Another source of bias in the flu vaccine trials could be originated from using placebo instead of no-intervention as controls; as placebo effect in this situations might reduce the magnitude of benefits.

It must be noted that these meta-analyses assessed the effectiveness of influenza vaccine in healthy individuals only. The vaccine is expected to have a greater protective effect on patients with multiple comorbidities and those who are immunocompromised. In addition, it is hard to factor in the role of herd immunity in a meta-analysis. Herd immunity refers to the protective effective of mass vaccination in prevention of the spread of contagious diseases. If sufficient people are immune to a disease through vaccination, non-immune individuals could indirectly be protected against the disease.5

Conclusion: Because of the evidence of significant benefit of flu vaccine in preventing influenza and influenza-like illness in healthy individuals and absence of serious adverse events, we have assigned a color recommendation of Green (Benefit > Harm) to this vaccine. The efficacy of the flu vaccine in preventing influenza is even more pronounced in healthy children and healthy elderly.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between and AEM.


Sally Liang, MD

Supervising editor: Shahriar Zehtabchi, MD


December 21, 2018