Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 2 (2), CD001269

Vaccines for Preventing Influenza in Healthy Adults

Affiliations
Review

Vaccines for Preventing Influenza in Healthy Adults

Vittorio Demicheli et al. Cochrane Database Syst Rev.

Abstract

Background: The consequences of influenza in adults are mainly time off work. Vaccination of pregnant women is recommended internationally. This is an update of a review published in 2014. Future updates of this review will be made only when new trials or vaccines become available. Observational data included in previous versions of the review have been retained for historical reasons but have not been updated due to their lack of influence on the review conclusions.

Objectives: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy adults, including pregnant women.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE (January 1966 to 31 December 2016), Embase (1990 to 31 December 2016), the WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017), as well as checking the bibliographies of retrieved articles.

Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. Previous versions of this review included observational comparative studies assessing serious and rare harms cohort and case-control studies. Due to the uncertain quality of observational (i.e. non-randomised) studies and their lack of influence on the review conclusions, we decided to update only randomised evidence. The searches for observational comparative studies are no longer updated.

Data collection and analysis: Two review authors independently assessed trial quality and extracted data. We rated certainty of evidence for key outcomes (influenza, influenza-like illness (ILI), hospitalisation, and adverse effects) using GRADE.

Main results: We included 52 clinical trials of over 80,000 people assessing the safety and effectiveness of influenza vaccines. We have presented findings from 25 studies comparing inactivated parenteral influenza vaccine against placebo or do-nothing control groups as the most relevant to decision-making. The studies were conducted over single influenza seasons in North America, South America, and Europe between 1969 and 2009. We did not consider studies at high risk of bias to influence the results of our outcomes except for hospitalisation.Inactivated influenza vaccines probably reduce influenza in healthy adults from 2.3% without vaccination to 0.9% (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.36 to 0.47; 71,221 participants; moderate-certainty evidence), and they probably reduce ILI from 21.5% to 18.1% (RR 0.84, 95% CI 0.75 to 0.95; 25,795 participants; moderate-certainty evidence; 71 healthy adults need to be vaccinated to prevent one of them experiencing influenza, and 29 healthy adults need to be vaccinated to prevent one of them experiencing an ILI). The difference between the two number needed to vaccinate (NNV) values depends on the different incidence of ILI and confirmed influenza among the study populations. Vaccination may lead to a small reduction in the risk of hospitalisation in healthy adults, from 14.7% to 14.1%, but the CI is wide and does not rule out a large benefit (RR 0.96, 95% CI 0.85 to 1.08; 11,924 participants; low-certainty evidence). Vaccines may lead to little or no small reduction in days off work (-0.04 days, 95% CI -0.14 days to 0.06; low-certainty evidence). Inactivated vaccines cause an increase in fever from 1.5% to 2.3%.We identified one RCT and one controlled clinical trial assessing the effects of vaccination in pregnant women. The efficacy of inactivated vaccine containing pH1N1 against influenza was 50% (95% CI 14% to 71%) in mothers (NNV 55), and 49% (95% CI 12% to 70%) in infants up to 24 weeks (NNV 56). No data were available on efficacy against seasonal influenza during pregnancy. Evidence from observational studies showed effectiveness of influenza vaccines against ILI in pregnant women to be 24% (95% CI 11% to 36%, NNV 94), and against influenza in newborns from vaccinated women to be 41% (95% CI 6% to 63%, NNV 27).Live aerosol vaccines have an overall effectiveness corresponding to an NNV of 46. The performance of one- or two-dose whole-virion 1968 to 1969 pandemic vaccines was higher (NNV 16) against ILI and (NNV 35) against influenza. There was limited impact on hospitalisations in the 1968 to 1969 pandemic (NNV 94). The administration of both seasonal and 2009 pandemic vaccines during pregnancy had no significant effect on abortion or neonatal death, but this was based on observational data sets.

Authors' conclusions: Healthy adults who receive inactivated parenteral influenza vaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence). They also probably experience less ILI following vaccination, but the degree of benefit when expressed in absolute terms varied across different settings. Variation in protection against ILI may be due in part to inconsistent symptom classification. Certainty of evidence for the small reductions in hospitalisations and time off work is low. Protection against influenza and ILI in mothers and newborns was smaller than the effects seen in other populations considered in this review.Vaccines increase the risk of a number of adverse events, including a small increase in fever, but rates of nausea and vomiting are uncertain. The protective effect of vaccination in pregnant women and newborns is also very modest. We did not find any evidence of an association between influenza vaccination and serious adverse events in the comparative studies considered in this review. Fifteen included RCTs were industry funded (29%).

Conflict of interest statement

Vittorio Demicheli: none known

Tom Jefferson (TJ) was a co‐recipient of a UK National Institute for Health Research grant (HTA – 10/80/01 Update and amalgamation of two Cochrane Reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children (www.nets.nihr.ac.uk/projects/hta/108001)). TJ receives royalties from his books published by Blackwells and Il Pensiero Scientifico Editore, Rome. TJ is occasionally interviewed by market research companies for anonymous interviews about phase I or II pharmaceutical products. In 2011 to 2013, TJ acted as an expert witness in a litigation case related to oseltamivir phosphate (Tamiflu; Roche) and in a labour case on influenza vaccines in healthcare workers in Canada. TJ acted as a consultant for Roche (1997‐99), GSK (2001‐2), and Sanofi‐Synthelabo (2003) for the antirhinoviral pleconaril, which was not approved by the US Food and Drug Administration. TJ was a consultant for IMS Health in 2013, and in 2014 he was retained as a scientific adviser to a legal team acting on the drug oseltamivir (Tamiflu; Roche). In 2014 to 2015, TJ was a member of two advisory boards for Boerhinger and is in receipt of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane Reviews. TJ has a potential financial conflict of interest in the investigation of the drug oseltamivir. TJ acted as an expert witness in a legal case involving the drug oseltamivir (Roche) and the vaccine Pandemrix (GSK). TJ was a member of an Independent Data Monitoring Committee for a Sanofi Pasteur clinical trial.

Eliana Ferroni: none known

Alessandro Rivetti: none known

Carlo Di Pietrantonj: none known

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 1 Influenza.
1.2
1.2. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 2 Influenza‐like illness.
1.3
1.3. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 3 Physician visits.
1.4
1.4. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 4 Days ill.
1.5
1.5. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 5 Times any drugs were prescribed.
1.6
1.6. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 6 Times antibiotic was prescribed.
1.7
1.7. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 7 Working days lost.
1.8
1.8. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 8 Hospitalisations.
1.9
1.9. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 9 Clinical cases (clinically defined without clear definition).
1.10
1.10. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 10 Local harms.
1.11
1.11. Analysis
Comparison 1 Inactivated parenteral influenza vaccine versus placebo or 'do nothing', Outcome 11 Systemic harms.
2.1
2.1. Analysis
Comparison 2 Live aerosol influenza vaccine versus placebo or 'do nothing', Outcome 1 Influenza.
2.2
2.2. Analysis
Comparison 2 Live aerosol influenza vaccine versus placebo or 'do nothing', Outcome 2 Influenza‐like illness.
2.3
2.3. Analysis
Comparison 2 Live aerosol influenza vaccine versus placebo or 'do nothing', Outcome 3 Influenza cases (clinically defined without clear definition).
2.4
2.4. Analysis
Comparison 2 Live aerosol influenza vaccine versus placebo or 'do nothing', Outcome 4 Local harms.
2.5
2.5. Analysis
Comparison 2 Live aerosol influenza vaccine versus placebo or 'do nothing', Outcome 5 Systemic harms.
3.1
3.1. Analysis
Comparison 3 Inactivated aerosol influenza vaccine versus placebo or 'do nothing', Outcome 1 Influenza.
3.2
3.2. Analysis
Comparison 3 Inactivated aerosol influenza vaccine versus placebo or 'do nothing', Outcome 2 Local harms.
3.3
3.3. Analysis
Comparison 3 Inactivated aerosol influenza vaccine versus placebo or 'do nothing', Outcome 3 Systemic harms.
4.1
4.1. Analysis
Comparison 4 Inactivated parenteral influenza vaccine versus placebo or 'do nothing' administered during pregnancy, Outcome 1 Influenza in mothers.
4.2
4.2. Analysis
Comparison 4 Inactivated parenteral influenza vaccine versus placebo or 'do nothing' administered during pregnancy, Outcome 2 Influenza‐like illness in mothers.
4.3
4.3. Analysis
Comparison 4 Inactivated parenteral influenza vaccine versus placebo or 'do nothing' administered during pregnancy, Outcome 3 Influenza in newborn.
4.4
4.4. Analysis
Comparison 4 Inactivated parenteral influenza vaccine versus placebo or 'do nothing' administered during pregnancy, Outcome 4 Influenza‐like illness in newborn.
5.1
5.1. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 1 Seasonal inactivated vaccine effectiveness in mothers ‐ pregnant women.
5.2
5.2. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 2 Seasonal inactivated vaccine effectiveness in newborns ‐ pregnant women.
5.3
5.3. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 3 Seasonal inactivated vaccine effectiveness in newborns ‐ pregnant women.
5.4
5.4. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 4 H1N1 vaccine ‐ safety ‐ pregnancy‐related outcomes ‐ pregnant women.
5.5
5.5. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 5 Seasonal vaccine ‐ safety ‐ pregnancy‐related outcomes ‐ pregnant women.
5.6
5.6. Analysis
Comparison 5 Inactivated parenteral influenza vaccine versus placebo ‐ cohort studies, Outcome 6 Seasonal vaccine containing H1N1.
6.1
6.1. Analysis
Comparison 6 Inactivated parenteral influenza vaccine versus placebo ‐ case‐control studies, Outcome 1 Effectiveness in newborns ‐ pregnant women (adjusted data).
6.2
6.2. Analysis
Comparison 6 Inactivated parenteral influenza vaccine versus placebo ‐ case‐control studies, Outcome 2 Seasonal vaccine safety ‐ pregnancy‐related outcomes (adjusted data).
7.1
7.1. Analysis
Comparison 7 Serious adverse events: Guillain‐Barré syndrome ‐ cohort studies, Outcome 1 Seasonal influenza vaccination and Guillain‐Barré syndrome.
8.1
8.1. Analysis
Comparison 8 Serious adverse events: Guillain‐Barré syndrome ‐ case‐control studies, Outcome 1 2009 to 2010 A/H1N1 ‐ general population (unadjusted data).
8.2
8.2. Analysis
Comparison 8 Serious adverse events: Guillain‐Barré syndrome ‐ case‐control studies, Outcome 2 2009 to 2010 A/H1N1 ‐ general population (adjusted data).
8.3
8.3. Analysis
Comparison 8 Serious adverse events: Guillain‐Barré syndrome ‐ case‐control studies, Outcome 3 Seasonal influenza vaccination general population (adjusted data).
9.1
9.1. Analysis
Comparison 9 Serious adverse events: demyelinating diseases (multiple sclerosis, optic neuritis) ‐ cohort studies, Outcome 1 Influenza vaccination (seasonal) ‐ demyelinating diseases (unadjusted data).
9.2
9.2. Analysis
Comparison 9 Serious adverse events: demyelinating diseases (multiple sclerosis, optic neuritis) ‐ cohort studies, Outcome 2 Influenza vaccination (H1N1) ‐ demyelinating diseases (unadjusted).
10.1
10.1. Analysis
Comparison 10 Serious adverse events: demyelinating diseases (multiple sclerosis, optic neuritis) ‐ case‐control studies, Outcome 1 Influenza vaccination (seasonal) ‐ general population ‐ demyelinating diseases (unadjusted data).
10.2
10.2. Analysis
Comparison 10 Serious adverse events: demyelinating diseases (multiple sclerosis, optic neuritis) ‐ case‐control studies, Outcome 2 Influenza vaccination (seasonal) ‐ general population ‐ multiple sclerosis (adjusted data).
10.3
10.3. Analysis
Comparison 10 Serious adverse events: demyelinating diseases (multiple sclerosis, optic neuritis) ‐ case‐control studies, Outcome 3 Influenza vaccination (seasonal) ‐ general population ‐ optic neuritis (adjusted data).
11.1
11.1. Analysis
Comparison 11 Serious adverse events: immune thrombocytopenic purpura ‐ cohort studies, Outcome 1 Seasonal influenza vaccine ‐ HR (adjusted data).
11.2
11.2. Analysis
Comparison 11 Serious adverse events: immune thrombocytopenic purpura ‐ cohort studies, Outcome 2 Seasonal influenza vaccine (unadjusted data).
12.1
12.1. Analysis
Comparison 12 Serious adverse events: immune thrombocytopenic purpura ‐ case‐control studies, Outcome 1 Seasonal influenza vaccine ‐ general population (adjusted data).
12.2
12.2. Analysis
Comparison 12 Serious adverse events: immune thrombocytopenic purpura ‐ case‐control studies, Outcome 2 Seasonal influenza vaccine ‐ general population (unadjusted data).
13.1
13.1. Analysis
Comparison 13 1968 to 1969 pandemic: inactivated polyvalent parenteral influenza vaccine versus placebo, Outcome 1 Influenza‐like illness.
13.2
13.2. Analysis
Comparison 13 1968 to 1969 pandemic: inactivated polyvalent parenteral influenza vaccine versus placebo, Outcome 2 Influenza.
13.3
13.3. Analysis
Comparison 13 1968 to 1969 pandemic: inactivated polyvalent parenteral influenza vaccine versus placebo, Outcome 3 Hospitalisations.
13.4
13.4. Analysis
Comparison 13 1968 to 1969 pandemic: inactivated polyvalent parenteral influenza vaccine versus placebo, Outcome 4 Pneumonia.
14.1
14.1. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 1 Influenza‐like illness.
14.2
14.2. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 2 Influenza.
14.3
14.3. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 3 Hospitalisations.
14.4
14.4. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 4 Pneumonia.
14.5
14.5. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 5 Working days lost.
14.6
14.6. Analysis
Comparison 14 1968 to 1969 pandemic: inactivated monovalent parenteral influenza vaccine versus placebo, Outcome 6 Days ill.
15.1
15.1. Analysis
Comparison 15 1968 to 1969 pandemic: inactivated polyvalent aerosol influenza vaccine versus placebo, Outcome 1 Influenza‐like illness.
16.1
16.1. Analysis
Comparison 16 1968 to 1969 pandemic: inactivated monovalent aerosol influenza vaccine versus placebo, Outcome 1 Influenza‐like illness.
17.1
17.1. Analysis
Comparison 17 1968 to 1969 pandemic: live aerosol influenza vaccine versus placebo, Outcome 1 Influenza cases (clinically defined without clear definition).
17.2
17.2. Analysis
Comparison 17 1968 to 1969 pandemic: live aerosol influenza vaccine versus placebo, Outcome 2 Complications (bronchitis, otitis, pneumonia).

Update of

  • Vaccines for Preventing Influenza in Healthy Adults
    V Demicheli et al. Cochrane Database Syst Rev (3), CD001269. PMID 24623315.
    Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women. No evidence of asso …

Similar articles

  • Vaccines for Preventing Influenza in Healthy Children
    T Jefferson et al. Cochrane Database Syst Rev 2 (2), CD004879. PMID 29388195. - Review
    In children aged between 3 and 16 years, live influenza vaccines probably reduce influenza (moderate-certainty evidence) and may reduce ILI (low-certainty evidence) over …
  • Vaccines for Preventing Influenza in the Elderly
    V Demicheli et al. Cochrane Database Syst Rev 2 (2), CD004876. PMID 29388197. - Review
    Older adults receiving the influenza vaccine may have a lower risk of influenza (from 6% to 2.4%), and probably have a lower risk of ILI compared with those who do not re …
  • Vaccines for Preventing Influenza in Healthy Adults
    V Demicheli et al. Cochrane Database Syst Rev (3), CD001269. PMID 24623315.
    Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women. No evidence of asso …
  • Influenza Vaccines in Immunosuppressed Adults With Cancer
    R Bitterman et al. Cochrane Database Syst Rev 2 (2), CD008983. PMID 29388675. - Review
    Observational data suggest lower mortality and infection-related outcomes with influenza vaccination. The strength of evidence is limited by the small number of studies a …
  • Vaccines for Preventing Influenza in Healthy Children
    T Jefferson et al. Cochrane Database Syst Rev 2012 (8), CD004879. PMID 22895945. - Review
    Influenza vaccines are efficacious in preventing cases of influenza in children older than two years of age, but little evidence is available for children younger than tw …
See all similar articles

Cited by 20 PubMed Central articles

See all "Cited by" articles

MeSH terms

Substances

Feedback