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