Vaccines for preventing influenza in healthy children

Tom Jefferson
1
, Alessandro Rivetti
2
, Anthony Harnden
3
, Carlo Di Pietrantonj
2
, Vittorio
Demicheli
4


1
Vaccines Field, The Cochrane Collaboration, Roma, Italy.
2
Servizio Regionale di
Riferimento per l'Epidemiologia, SSEpi-SeREMI - Cochrane Vaccines Field, Azienda
Sanitaria Locale ASL AL, Alessandria, Italy.
3
Department of Primary Health Care, Institute
of Health Sciences, Oxford, UK.
4
Health Councillorship - Servizio Regionale di Riferimento
per l'Epidemiologia, SSEpi-SeREMI - Cochrane Vaccines Field, Regione Piemonte -
Azienda Sanitaria Locale ASL AL, Torino, Italy

Contact address: Tom Jefferson, Vaccines Field, The Cochrane Collaboration, Via Adige
28a, Anguillara Sabazia, Roma, 00061, Italy. jefferson.tom@gmail.com. jefferson@assr.it;
jefferson.tom@gmail.com. (Editorial group: Cochrane Acute Respiratory Infections Group.)

Cochrane Database of Systematic Reviews, Issue 4, 2008 (Status in this issue: Unchanged)
Copyright 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD004879.pub3
This version first published online: 23 April 2008 in Issue 2, 2008. Last assessed as up-to-
date: 29 September 2007

This record should be cited as: Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C,
Demicheli V. Vaccines for preventing influenza in healthy children. Cochrane Database of
Systematic Reviews 2008, Issue 2. Art. No.: CD004879. DOI:
10.1002/14651858.CD004879.pub3.

Abstract
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
old.
Objectives
To appraise all comparative studies evaluating the effects of influenza vaccines in healthy
children; assess vaccine efficacy (prevention of confirmed influenza) and effectiveness
(prevention of influenza-like illness) and document adverse events associated with influenza
vaccines.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
Library 2007, issue 3); OLD MEDLINE (1950 to 1965); MEDLINE (1966 to September
2007); EMBASE (1974 to September 2007); Biological Abstracts (1969 to September 2007);
and Science Citation Index (1974 to September 2007).
Selection criteria
Randomised controlled trials (RCTs), cohort and case-control studies of any influenza
vaccine in healthy children under 16 years of age.
Data collection and analysis
Two review authors independently assessed trial quality and extracted data.
Main results
Fifty-one studies with 294,159 observations were included. Sixteen RCTs and 18 cohort
studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live
vaccines showed an efficacy of 82% (95% confidence interval (CI) 71% to 89%) and an
effectiveness of 33% (95% CI 28% to 38%) in children older than two compared with
placebo or no intervention. Inactivated vaccines had a lower efficacy of 59% (95% CI 41% to
71%) than live vaccines but similar effectiveness: 36% (95% CI 24% to 46%). In children
under two, the efficacy of inactivated vaccine was similar to placebo. Variability in study
design and presentation of data was such that a meta-analysis of safety outcome data was not
feasible. Extensive evidence of reporting bias of safety outcomes from trials of live
attenuated vaccines impeded meaningful analysis.
Authors' conclusions
Influenza vaccines are efficacious in children older than two but little evidence is available
for children under two. There was a marked difference between vaccine efficacy and
effectiveness. No safety comparisons could be carried out, emphasizing the need for
standardisation of methods and presentation of vaccine safety data in future studies. It was
surprising to find only one study of inactivated vaccine in children under two years, given
current recommendations to vaccinate healthy children from six months old in the USA and
Canada. If immunisation in children is to be recommended as a public health policy, large-
scale studies assessing important outcomes and directly comparing vaccine types are urgently
required.

Plain language summary

Vaccines for preventing influenza in healthy children
Children and the elderly are the two age groups that appear to have the most complications
following an influenza infection. Influenza has a viral origin and often results in an acute
respiratory illness affecting the lower or upper parts respiratory tract, or both. Viruses are
mainly of two subtypes (A or B) and spread periodically during the autumn-winter months.
Many other viruses however, can also cause illness of the respiratory tract.

Diffusion and severity of the disease could be very different during different epidemics.
Efforts to contain epidemic diffusion rely mainly on widespread vaccination. Recent policy
from several internationally-recognised institutions, recommend immunisation of healthy
children between 6 and 23 month of age (together with their contacts) as a public health
measure.

The review authors found that in children aged from two years, nasal spray vaccines made
from weakened influenza viruses were better at preventing illness caused by the influenza
virus (82% of illnesses were prevented) than injected vaccines made from the killed virus
(59%). Neither type was particularly good at preventing 'flu-like illness' caused by other
types of viruses (33% and 36% respectively). In children under the age of two, the efficacy of
inactivated vaccine was similar to placebo. It was not possible to analyse the safety of
vaccines from the studies due to the lack of standardisation in the information given but very
little information was found on the safety of inactivated vaccines, the most commonly used
vaccine, in young children.