extending the seasonal influenza immunisation programme to ... · case fatality ratio (deaths /...
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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
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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%)
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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
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Stopping the transmission of influenza
and protecting the most vulnerable
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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
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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
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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
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Dead Dead
Hospitalized
Medically attended
Symptomatic
Infected
Knowledge
fundamental
for modelling
Severity pyramid
Only the top is
observed by
surveillance
H3N2
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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
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Incidence of influenza admission by age and
risk group /100,000 (2000/01 to 2007/08)
12
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Case fatality ratio (deaths / 1000 influenza
admissions) by age and risk group
13
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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
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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
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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
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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
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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
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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
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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
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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