NIHR DC Discover

NIHR Signal Vaccination likely to reduce influenza in healthy children

Published on 22 May 2018

doi: 10.3310/signal-00595

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.

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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 Choices. Flu. London: Department of Health; updated 2017.

NHS Choices. Vaccinations: annual flu vaccine (2-8 years including children in reception and school years 1-4). London: Department of Health; updated 2016.

NHS Choices. Vaccinations: children’s flu vaccine FAQs. London: Department of Health; updated 2016.

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.

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 Choices. Flu. London: Department of Health; updated 2017.

NHS Choices. Vaccinations: annual flu vaccine (2-8 years including children in reception and school years 1-4). London: Department of Health; updated 2016.

NHS Choices. Vaccinations: children’s flu vaccine FAQs. London: Department of Health; updated 2016.

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.

Vaccines for preventing influenza in healthy children

Published on 2 February 2018

Jefferson, T.,Rivetti, A.,Di Pietrantonj, C.,Demicheli, V.

Cochrane Database Syst Rev Volume 2 , 2018

BACKGROUND: The consequences of influenza in children and adults are mainly absenteeism from school and work. However, the risk of complications is greatest in children and people over 65 years of age. This is an update of a review published in 2011. 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. OBJECTIVES: To assess the effects (efficacy, effectiveness, and harm) of vaccines against influenza in healthy children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 12), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1966 to 31 December 2016), Embase (1974 to 31 December 2016), WHO International Clinical Trials Registry Platform (ICTRP; 1 July 2017), and ClinicalTrials.gov (1 July 2017). SELECTION CRITERIA: Randomised controlled trials comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy children under 16 years. Previous versions of this review included 19 cohort and 11 case-control studies. We are no longer updating the searches for these study designs but have retained the observational studies for historical purposes. DATA COLLECTION AND ANALYSIS: Review authors independently assessed risk of bias and extracted data. We used GRADE to rate the certainty of evidence for the key outcomes of influenza, influenza-like illness (ILI), complications (hospitalisation, ear infection), and adverse events. Due to variation in control group risks for influenza and ILI, absolute effects are reported as the median control group risk, and numbers needed to vaccinate (NNVs) are reported accordingly. For other outcomes aggregate control group risks are used. MAIN RESULTS: We included 41 clinical trials (> 200,000 children). Most of the studies were conducted in children over the age of two and compared live attenuated or inactivated vaccines with placebo or no vaccine. Studies were conducted over single influenza seasons in the USA, Western Europe, Russia, and Bangladesh between 1984 and 2013. Restricting analyses to studies at low risk of bias showed that influenza and otitis media were the only outcomes where the impact of bias was negligible. Variability in study design and reporting impeded meta-analysis of harms outcomes.Live attenuated vaccinesCompared with placebo or do nothing, live attenuated influenza vaccines probably reduce the risk of influenza infection in children aged 3 to 16 years from 18% to 4% (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.41; 7718 children; moderate-certainty evidence), and they may reduce ILI by a smaller degree, from 17% to 12% (RR 0.69, 95% CI 0.60 to 0.80; 124,606 children; low-certainty evidence). Seven children would need to be vaccinated to prevent one case of influenza, and 20 children would need to be vaccinated to prevent one child experiencing an ILI. Acute otitis media is probably similar following vaccine or placebo during seasonal influenza, but this result comes from a single study with particularly high rates of acute otitis media (RR 0.98, 95% CI 0.95 to 1.01; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. Vaccinating children may lead to fewer parents taking time off work, although the CI includes no effect (RR 0.69, 95% CI 0.46 to 1.03; low-certainty evidence). Data on the most serious consequences of influenza complications leading to hospitalisation were not available. Data from four studies measuring fever following vaccination varied considerably, from 0.16% to 15% in children who had live vaccines, while in the placebo groups the proportions ranged from 0.71% to 22% (very low-certainty evidence). Data on nausea were not reported.Inactivated vaccinesCompared with placebo or no vaccination, inactivated vaccines reduce the risk of influenza in children aged 2 to 16 years from 30% to 11% (RR 0.36, 95% CI 0.28 to 0.48; 1628 children; high-certainty evidence), and they probably reduce ILI from 28% to 20% (RR 0.72, 95% CI 0.65 to 0.79; 19,044 children; moderate-certainty evidence). Five children would need to be vaccinated to prevent one case of influenza, and 12 children would need to be vaccinated to avoid one case of ILI. The risk of otitis media is probably similar between vaccinated children and unvaccinated children (31% versus 27%), although the CI does not exclude a meaningful increase in otitis media following vaccination (RR 1.15, 95% CI 0.95 to 1.40; 884 participants; moderate-certainty evidence). There was insufficient information available to determine the effect of vaccines on school absenteeism due to very low-certainty evidence from one study. We identified no data on parental working time lost, hospitalisation, fever, or nausea.We found limited evidence on secondary cases, requirement for treatment of lower respiratory tract disease, and drug prescriptions. One brand of monovalent pandemic vaccine was associated with a sudden loss of muscle tone triggered by the experience of an intense emotion (cataplexy) and a sleep disorder (narcolepsy) in children. Evidence of serious harms (such as febrile fits) was sparse. AUTHORS' CONCLUSIONS: 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 a single influenza season. In this population inactivated vaccines also reduce influenza (high-certainty evidence) and may reduce ILI (low-certainty evidence). For both vaccine types, the absolute reduction in influenza and ILI varied considerably across the study populations, making it difficult to predict how these findings translate to different settings. We found very few randomised controlled trials in children under two years of age. Adverse event data were not well described in the available studies. Standardised approaches to the definition, ascertainment, and reporting of adverse events are needed. Identification of all global cases of potential harms is beyond the scope of this review.

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.

Expert commentary

Parents of healthy children and their clinicians probably overestimate the benefits of annual flu vaccination.

The number needed to vaccinate (NNV) ‘bang’ of a flu shot is like a reverse of Russian roulette with about five or six blank shots and only one shot being effective at prevention of flu.

Despite a continuing lack of good information about the number needed to harm, the dire consequences of bad flu in a healthy child probably still make vaccination a reasonable recommendation for parents.

Terry Kemple, GP

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