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Extending the seasonal influenza
immunisation programme
to school-aged children:
the rationale for the decision in
the United Kingdom
Mary Ramsay Public Health England
Seasonal trivalent inactivated vaccine
(TIV) programme in the UK
• All high risk groups under 65 years
• All 65+ year olds
• Problems :
– efficacy of TIV in elderly and the very young is
poor
– Most vulnerable groups are the elderly and the
very young
– Achieving and sustaining high coverage (EU
target of 75%)
Year 2012/13 2013/14
Under 65 at risk
51.3% 52.3%
Pregnant women
40.3% 39.8%
Health care workers
45.9% 54.8%
Uptake in high risk
groups, England
Stopping the transmission of influenza
and protecting the most vulnerable
Extensions to current programme
• Extend to low-risk:
– 2-4 years
– 50-64 years
– 5-16 years
– 2-4 & 50-64 years
– 2-16 years
– 2-16 & 50-64 years
– 2-64 years
• Coverage assumed to be sustained at 50% in
low-risk groups
Net additional
cost
£282m
Increasing
cost
£14m
Modelling approach
• Estimate the current burden of seasonal influenza by
age for high and low risk groups
• Build a transmission model that incorporates • the necessary age groups, separately for high and low risk people
• captures the seasonal patterns by age and subtype (H1, H3 and B)
under the existing programme
• predicts the direct and indirect effects of the proposed programmatic
additions
• Use the transmission model outputs to estimate • the costs of the different programme extensions
• the savings in health care costs and QALYs
Mathematical models of infectious
diseases
• Compartmental models based on the
Susceptible-Exposed-Infected-Recovered
(SEIR) structure
• Include age structure and risk groups
• “Easy” to produce a model, difficult to fit to
surveillance data for influenza
– Surveillance only detects serious outcomes
– Not all influenza like illness is due to influenza
infection
Dead Dead
Hospitalized
Medically attended
Symptomatic
Infected
Knowledge
fundamental
for modelling
Severity pyramid
Only the top is
observed by
surveillance
H3N2
Complex mathematical and
statistical problem
• Evidence synthesis linking mathematical
modelling is to linked different data sources
using Bayesian approaches
• Build dynamic transmission model and
probabilistic observation model
– Estimate incidence by main type over 14 seasons
• Incorporate risk of various outcomes (e.g.
hospitalisations, deaths)
– By age and by risk group
– By influenza type
Incidence of influenza admission by age and
risk group /100,000 (2000/01 to 2007/08)
12
Case fatality ratio (deaths / 1000 influenza
admissions) by age and risk group
13
Results of cost-effectiveness
analysis
Increment ICER
(£/QALY)
% of iterations where
< £20,000/QALY
Current → 2-4 y 2647 100
2-4 y → 5-16 y 1611 100
5-16 y → 2-16 y 3494 100
2-16 y →
2-16 y & 50-64 y 8458 86
2-16 y & 50-64 y
→ 2-64 y 9330 81
Summary of cost
effectiveness
• Schools based programme has potential to
dramatically alter the transmission of influenza
• All options including school children were highly cost effective
• Superior cost-effectiveness to existing high risk and
elderly (>65y) programme
• Indirect protection from interruption of transmission in schools
• Impact even with modest coverage (>30%)
• Potential to prevent millions of infections and
thousands deaths
• Estimated to avert around 2 deaths for every 1000
vaccines delivered
UK Childhood Influenza
Programme
• In 2012 the UK Joint Committee on Vaccination and
Immunisation (JCVI) recommended extending
influenza vaccination to all children aged 2-17 years
• Programme recommended on the basis of using a
single dose of trivalent live attenuated vaccine – Higher efficacy in children, particularly after only a single dose
– Higher acceptability of intranasal administration with parents and
careers
– Workload in a single dose programme reduced
– Potential to provide coverage against circulating strains that have
drifted from those contained in the vaccine
– Replicate natural exposure/infection to induce potentially better
immune memory to influenza
Influenza programme 2013/14,
England
• Two and three year olds in general
practice
– Vaccination delivered by practice nurses
• Pilots in primary school children (aged 4-
10 years) in seven local areas
– Six areas had school based programmes
delivered by qualified nurses
– Seventh area delivered by pharmacists in
community settings
Parental and professional
attitudes to LAIV
• Well accepted – refusal in pilots around 8%
– Some difficulty with contra-indications
– No serious reactions reported
• Only concern expressed was about porcine
gelatine content of vaccine
– Local media interest and some Muslim cleric
resistance
– PHE/DH decision to NOT offer inactivated vaccine
to healthy children as alternative
– Lower uptake observed in schools with high
Muslim population
2013/2014 influenza coverage
• Two and three year olds in general practice
– 42.6% in all 2 year olds (>290,000 not in risk group)
– 39.6% in all 3 year olds (>270,000 not in risk group)
– > 500,000 children across England vaccinated
• Primary school children (aged 4-10 years) in
seven local areas
– Coverage ranged from 37.2 – 70.8% by area
– > 100,000 children vaccinated with LAIV
Summary of UK experience in
2013/14
• Live attenuated vaccine was acceptable to
parents and health care workers
• Scale of implementation in relatively short
timescale is huge
– Major clinical and administrative capacity required
– School support is essential
• Roll out plan has been slowed down
– 2, 3, and 4 year olds in 2014/15 (continue pilots)
– School years 1-3 in 2015/16
Acknowledgments
• Stefan Flasche, Anton Camacho, John Edmunds (LSHTM)
• Marc Baguelin, Richard Pebody, Louise Letley, Joanne Yarwood (Public Health England)
• Screening and Immunisation Teams in pilot areas