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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

In healthy children aged two to 16, vaccines are likely to reduce laboratory-confirmed cases of influenza and may reduce the risk of influenza-like illness compared to placebo. Seven children need to receive the live vaccine to prevent one case of confirmed influenza. Twenty children need to be vaccinated to prevent one case of influenza-like illness.

This updated Cochrane review included 41 trials of either live attenuated (weakened) or inactivated influenza vaccines, with over 200,000 participants. The evidence gave a moderate to high level of certainty about their effects on influenza, but only a low certainty about the effect on influenza-like illness due to problems in reporting and data capture.

The finding supports the benefits of the existing vaccination programme for healthy children, although there is still a lack of clear evidence on the impact on important outcomes such as hospitalisation for influenza, or adverse events.

Why was this study needed?

Influenza is an acute disease caused by a viral infection of the respiratory tract; symptoms typically resolve within a week. At the peak of the 2016-17 influenza season 0.58% of all GP consultations and 1.5% of NHS 111 calls were for cold or influenza symptoms. This was equivalent to 18 per 100,000 population being affected.

In children, influenza typically results in a short absence from school, and this may require their parents or carers to take time off work. Common complications of influenza include bronchitis and middle ear infection (otitis media). Less commonly, severe complications such as pneumonia and meningitis can be fatal. Healthy children aged under five are more likely to be admitted to hospital with influenza than any other age group.

The current review aimed to provide an updated assessment of the efficacy, effectiveness and safety of vaccinating healthy children against influenza.

What did this study do?

This was an update of a review and meta-analysis, comparing any influenza vaccine with placebo or no vaccination. It added two new trials published since 2011, bringing the total to 41. Only one multicentre trial included children from the UK. Eighteen trials reported efficacy or effectiveness and 23 trials assessed safety only.

The overall quality of reporting in studies was low. The only outcomes where bias was not judged to affect the results were confirmed influenza and otitis media. Wide variation in rates of influenza and influenza-like illness was reported across studies reducing our confidence in the estimates of effect.

Recent updates have not changed the review’s conclusions, so its findings are now considered to be stable. Observational data in the previous review (based on 33 studies) have not been updated because of their lack of influence on the review conclusions. It will only be updated in future if new randomised evidence becomes available.

What did it find?

  • In children aged three to 16 years old live attenuated vaccines reduced risk of laboratory-confirmed flu from a median of 18% to 4% compared with placebo (risk difference [RD] -14%, 95% confidence interval [CI] -16% to -12%; risk ratio [RR] 0.22, 95% CI 0.11 to 0.41; seven trials, 7,718 children; moderate certainty evidence). The number needed to vaccinate (NNV) to prevent a single case of flu was seven children.
  • Live attenuated vaccines also reduced risk of flu-like illness from a median of 17% to 12% compared with placebo (RD -5%, 95% CI -7% to -4%; RR 0.69, 95% CI 0.60 to 0.80; seven trials, 124,606 children; low certainty evidence). The NNV to prevent a single case of flu-like illness was 20 children.
  • In children aged two to 16 years old inactivated vaccines also reduced the risk of laboratory-confirmed flu (five trials). The NNV to prevent a single case of flu was five children. These inactivated vaccines reduced the risk of flu-like illness too. The NNV to prevent a single case of flu-like illness was 12 children.
  • Neither type of vaccine significantly reduced the risk of developing otitis media (moderate certainty evidence) or the risk of absence from school. None of the trials assessed need for hospitalisation due to complications of flu. Despite many trials assessing safety, data on adverse events was not well reported.

What does current guidance say on this issue?

In 2012, the Joint Committee on Vaccination and Immunisation recommended a single dose of live attenuated intranasal vaccine for all children between two and 17 years of age. This is being rolled out gradually, starting with younger age groups. In the 2018-19 influenza season vaccination will be offered to:

  • all two to four-year-olds (usually vaccinated in their general practice by a nurse)
  • all primary school children from reception up to Year five (usually vaccinated in school).

In some areas, vaccination will also be offered to older primary school children.

NICE released draft guidance on increasing influenza vaccination uptake for consultation in June 2017; the date for final publication is to be confirmed.

What are the implications?

The review supports live vaccination as recommended in the UK and confirms that laboratory measured flu in healthy children, and to a lesser extent flu-like illness, is reduced. The continuing lack of evidence on serious complications such as hospitalisation warrants further study.

Provisional figures for 1st September 2017 to 31st January 2018 suggest that almost two million children of primary school age received the flu vaccine in this period.

Based on the NNVs reported in the review, this could mean that about 285,000 cases of confirmed laboratory flu and 99,000 cases of flu-like illness each year can be prevented, although the absolute reduction is likely to vary in different settings.

Citation and Funding

Jefferson T, Rivetti A, Di Pietrantoni C, Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2018;(2):CD004879.

No external sources of support were reported. Internal sources included a UK Medical Research Council grant and the Local Health Authority in Piemonte in Italy.

 

Bibliography

Jefferson T, Rivetti A, Di Pietrantoni C, Demicheli V. Why have three long-running Cochrane Reviews on influenza vaccines been stabilised? Cochrane Community Blog; 2018.

NHS website. Flu. London: Department of Health and Social Care; updated 2017.s

NHS website. Vaccinations: children and teens. London: Department of Health and Social Care; updated 2016.

NHS website. Vaccinations: children’s flu vaccine FAQs. London: Department of Health and Social Care; updated 2018.

NICE. Flu vaccination: increasing uptake. In development GID-PHG96. London: National Institute for Health and Care Excellence; 2017.

PHE. Influenza: the green book, chapter 19. London: Public Health England; 2013.

PHE. National flu immunisation programme 2018 to 2019 letter. London: Public Health England; 2018.

PHE. National Childhood Influenza Vaccination Programme 2017 to 2018: Seasonal influenza vaccine uptake for children of primary school age. London: Public Health England; 2018.

JCVI. JCVI statement on the nasal spray flu vaccine. London: Joint Committee on Vaccination and Immunisation; 2016.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

 

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Definitions

Confirmed influenza – Having one or more influenza viruses identified by one or more methods (serological, culture or PCR).

Influenza-like illness – Having symptoms of influenza (such as fever, headache, aches, pains, cough, and runny nose) but no laboratory confirmation of infection with influenza virus(es). These symptoms can be caused by many different viruses, and it is not possible to differentiate between influenza and these other infections clinically (i.e. based on symptoms alone without laboratory tests). This outcome (influenza-like illness) is likely to be more clinically relevant as the cause of this type of symptoms may not be routinely assessed.

 

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