Review aim
The aim of this Cochrane Review, first published in 2006, was to summarise research that looks at the effects of immunising the elderly (those aged 65 years or older) with influenza vaccine during influenza seasons. We used information from randomised trials comparing influenza vaccine with dummy vaccine or with nothing. The influenza vaccines were prepared by treating influenza viruses with a chemical that kills the virus (inactivated virus), and the vaccination was given by injection through the skin. We were interested in showing the effects of vaccines on reducing the number of elderly with confirmed influenza, the number who had influenza-like symptoms such as headache, high temperature, cough, and muscle pain (influenza-like illness, of ILI), and harms from vaccination. We looked for evidence of the impact of influenza or ILI such as hospital admission, complications, and death. We will update this review in the future only when new trials or vaccines become available.
Observational data from 67 studies included in previous versions of the review have been retained for historical reasons but have not been updated because of their lack of influence on the review conclusions.
What was studied in this review?
Over 200 viruses cause ILI, producing the same symptoms (fever, headache, aches, pains, cough, and runny nose). Without laboratory tests, doctors cannot distinguish between viruses, as they last for days and rarely lead to serious illness. At best, vaccines are only effective against influenza A and B, which represent about 5% of all circulating viruses. Inactivated vaccine is prepared by treating influenza viruses with a specific chemical agent that 'kills' the virus. Final preparations may contain either the complete viruses (whole-virion vaccine) or the active part of them (split or subunit vaccines). These vaccines are typically administered by injection through the skin. The virus strains contained in the vaccine are usually those that are expected to circulate in the following epidemic seasons (two type A and one or two B strains), which are recommended by the World Health Organization (seasonal vaccine). Pandemic vaccine contains only the virus strain that is responsible for the pandemic (e.g. the type A H1N1 for the 2009 to 2010 pandemic).
Key messages
Inactivated vaccines can reduce the proportion of elderly who have influenza and ILI. Data on deaths were sparse, and we found no data on hospitalisations due to complications. However, variation in the results of studies means we cannot be certain about how big a difference these vaccines will make across different seasons.
Main results
We found eight randomised controlled trials (over 5000 people), of which four assessed harms. The studies were conducted in community and residential care settings in Europe and the USA between 1965 and 2000.
Older adults receiving the influenza vaccine may experience less influenza over a single season, from 6% to 2.4%, meaning that 30 people would need to be vaccinated with inactivated influenza vaccines to avoid one case of influenza. Older adults also probably experience less ILI, from 6% to 3.5%, meaning that 42 people would need to be vaccinated to prevent one case of ILI. The amount of information on pneumonia and mortality was limited. Data were insufficient to be certain about the effect of vaccines on mortality. No cases of pneumonia occurred in one study that reported this outcome, and no data on hospitalisations were reported. We do not have enough information to assess harms relating to fever and nausea in this population.
The impact of influenza vaccines in older people is modest, irrespective of setting, outcome, population, and study design.
How up to date is this review?
The evidence is current to 31 December 2016.
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 receive a vaccination over the course of a single influenza season (from 6% to 3.5%). We are uncertain how big a difference these vaccines will make across different seasons. Very few deaths occurred, and no data on hospitalisation were reported. No cases of pneumonia occurred in one study that reported this outcome. We do not have enough information to assess harms relating to fever and nausea in this population.
The evidence for a lower risk of influenza and ILI with vaccination is limited by biases in the design or conduct of the studies. Lack of detail regarding the methods used to confirm the diagnosis of influenza limits the applicability of this result. The available evidence relating to complications is of poor quality, insufficient, or old and provides no clear guidance for public health regarding the safety, efficacy, or effectiveness of influenza vaccines for people aged 65 years or older. Society should invest in research on a new generation of influenza vaccines for the elderly.
The consequences of influenza in the elderly (those age 65 years or older) are complications, hospitalisations, and death. The primary goal of influenza vaccination in the elderly is to reduce the risk of death among people who are most vulnerable. This is an update of a review published in 2010. 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 because of their lack of influence on the review conclusions.
To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in the elderly.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 11), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1966 to 31 December 2016); Embase (1974 to 31 December 2016); Web of Science (1974 to 31 December 2016); CINAHL (1981 to 31 December 2016); LILACS (1982 to 31 December 2016); WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017); and ClinicalTrials.gov (1 July 2017).
Randomised controlled trials (RCTs) and quasi-RCTs assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. We considered any influenza vaccine given independently, in any dose, preparation, or time schedule, compared with placebo or with no intervention. Previous versions of this review included 67 cohort and case-control studies. The searches for these trial designs are no longer updated.
Review authors independently assessed risk of bias and extracted data. We rated the certainty of evidence with GRADE for the key outcomes of influenza, ILI, complications (hospitalisation, pneumonia), and adverse events. We have presented aggregate control group risks to illustrate the effect in absolute terms. We used them as the basis for calculating the number needed to vaccinate to prevent one case of each event for influenza and ILI outcomes.
We identified eight RCTs (over 5000 participants), of which four assessed harms. The studies were conducted in community and residential care settings in Europe and the USA between 1965 and 2000. Risk of bias reduced our certainty in the findings for influenza and ILI, but not for other outcomes.
Older adults receiving the influenza vaccine may experience less influenza over a single season compared with placebo, from 6% to 2.4% (risk ratio (RR) 0.42, 95% confidence interval (CI) 0.27 to 0.66; low-certainty evidence). We rated the evidence as low certainty due to uncertainty over how influenza was diagnosed. Older adults probably experience less ILI compared with those who do not receive a vaccination over the course of a single influenza season (3.5% versus 6%; RR 0.59, 95% CI 0.47 to 0.73; moderate-certainty evidence). These results indicate that 30 people would need to be vaccinated to prevent one person experiencing influenza, and 42 would need to be vaccinated to prevent one person having an ILI.
The study providing data for mortality and pneumonia was underpowered to detect differences in these outcomes. There were 3 deaths from 522 participants in the vaccination arm and 1 death from 177 participants in the placebo arm, providing very low-certainty evidence for the effect on mortality (RR 1.02, 95% CI 0.11 to 9.72). No cases of pneumonia occurred in one study that reported this outcome (very low-certainty evidence). No data on hospitalisations were reported. Confidence intervaIs around the effect of vaccines on fever and nausea were wide, and we do not have enough information about these harms in older people (fever: 1.6% with placebo compared with 2.5% after vaccination (RR 1.57, 0.92 to 2.71; moderate-certainty evidence)); nausea (2.4% with placebo compared with 4.2% after vaccination (RR 1.75, 95% CI 0.74 to 4.12; low-certainty evidence)).