Vaccination strategies to reduce the burden of seasonal
Vaccination strategies to reduce the burden of seasonal influenza Richard Roberts Vaccine Preventable Disease Programme April 2018
Strategies to minimise impact of seasonal influenza Multiple approaches 1. Achieve and maintain high vaccination coverage in at-risk groups 2. Prevent transmission to vulnerable groups 3. Prophylaxis and early treatment with antivirals 4. (Manufacture / match vaccine strains to those circulating) 5. LAIV 4 programme in 2 -11 year olds 6. Is QIV worth using? For who? Effectiveness? Is it cost effective? 7. What is evidence for and role of adjuvanted (and high potency) flu vaccines? Influenza strategies
What we know already Flu vaccines are moderately effective • Flu vaccination reduces the risk of influenza by 40% to 60% in the general population when circulating flu viruses are well-matched to the flu vaccine • In general, flu vaccines tend to work better against influenza B and influenza A(H 1 N 1) viruses • Flu vaccines offer lower protection against influenza A(H 3 N 2) viruses Influenza strategies
2017/18 mid-season flu vaccine effectiveness (at 14 Jan) Flu B cross protection, low A(H 3 N 2) effectiveness • Overall adjusted VE was 24. 6% (95% C. I. -9. 8, 48. 2) for all vaccines against all laboratory confirmed influenza like illness (ILI) • Overall Flu B VE 54. 2% (24. 4 -72. 3) • Overall A(H 3 N 2) VE -26. 6% (-111, 24. 1) • LAIV 4 in 2 -17 year olds VE 53. 1% (-56. 2, 85. 9) • Adults IIV VE 17. 7% (-23. 0, 44. 9) These are preliminary results, end of season estimates awaited Influenza strategies
Quadrivalent flu vaccines QIV, LAIV 4 More clinically effective, cost effective under 65 years • PHE found QIV and LAIV 4 were more clinically effective vs trivalent • The cost-effectiveness of the programme is dependent on a) the choice of target cohort and b) the cost of the vaccine • The paediatric programme is cost-effective with an increased cost below £ 6. 36 per dose • For at risk individuals younger than 65 years the maximum incremental cost per dose is £ 1. 84 • For those age 65 years and over the increased cost per does would need to be less than £ 0. 20 to be cost effective Influenza strategies Thorrington et al, BMC Medicine (2017) 15: 166 DOI 10. 1186/s 12916 -017 -0932 -3
Influenza burden in children Globally A systematic review in 2008 globally of around 8 million children, estimated that there were annually in children <5 years of age: • 90 million (95% CI 49– 162) cases of influenza • 20 million (95% CI 13– 32) cases of influenza-associated acute lower respiratory infections (ALRI) • 1– 2 million cases of severe ALRI • 28, 000– 111, 500 deaths from influenza (around 1% of all deaths) • Universal child vaccination against flu is not a WHO policy Influenza strategies
Number of cases prevented for 65+ vs adding 5 -16 y extension England Wales Influenza strategies Baguelin et al, PLOS Medicine 2013 10: e 1001527 http: //journals. plos. org/plosmedicine/article? id=10. 1371/journal. pmed. 1001527
Effectiveness of LAIV vs TIV in children LAIV more effective Influenza strategies Source: Richard Pebody et al 2016 http: //www. who. int/immunization/research/meetings_workshops/Richard_Pebody_L AIV_meeting_2016_Geneva. pdf? ua=1
Impact of LAIV on community influenza burden Population wide impact Influenza strategies Source: Richard Pebody et al 2016 http: //www. who. int/immunization/research/meetings_workshops/Richard_Pebody_L AIV_meeting_2016_Geneva. pdf? ua=1
Effectiveness of LAIV kept under review National differences • Lower LAIV effectiveness against A(H 1 N 1)pdm 09 than other flu types • Led to change in policy in US • Important to keep effectiveness under review Influenza strategies Pebody R et al BMJ Arch Childhood Dis 2017 http: //adc. bmj. com/content/archdischild/early/2017/08/30/archdischild-2016312165. full. pdf
Seroconversion after flu vaccine in the elderly is poor Antibody responses age in 20 s vs 60 s/70 s/80 s Influenza strategies Panda et al, J Immunol 2010, 184: 2518 -2527 www. jimmunol. org/cgi/doi/10. 4049/jimmunol. 0901022
TIV vaccine not effective against A(H 3 N 2) over 60 years Global metanalysis of 56 studies 2004 -2015 • 56 studies in the meta-analysis (from 3368 publications) • Pooled VE: A(H 3 N 2) was 33% (95% CI 26– 39), flu B 54% (46– 61) for type B, A(H 1 N 1)pdm 09 61% (57– 65), A(H 1 N 1) 67% (29– 85) • Among adults aged over 60 years, pooled VE against A(H 3 N 2) was 24% (− 6 to 45), against flu B 63% (33– 79) and against A(H 1 N 1)pdm 09 was 62% (36– 78). Influenza strategies Bellongia et al, Lancet ID 2016; 16: 942– 951 https: //doi. org/10. 1016/S 1473 -3099(16)00129 -8
TIV vaccine not effective at all over 75 years Pooled UK data 2010/11 – 2016/17 • PHE conducted an age stratified analysis of pooled primary care data since 2010/11 which showed: • Significant effectiveness in the 65 -74 age group for all influenza, A(H 1 N 1)pdm 09, flu B and evidence of protection against A(H 3 N 2) • No significant protection at all in those age 75 and over across all seasons and all the influenza virus types Influenza strategies Green Book 2018
The first study: a. TIV vs TIV in 65+ cohort study Lombardy Northern Italy 2006 -2009 • Prospective cohort, hospitalizations for influenza or pneumonia • Regression analysis and adjustment for age and comorbidities • 107, 661 records covering 170, 988 person-seasons • Recipients of a. TIV were older with more comorbidities • Adjusted relative effectiveness of a. TIV v TIV by time window: Influenza strategies Mannino Am J Epidemiol. 2012 Sep 15; 176(6): 527– 533 https: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 3447603/
Effectiveness a. TIV vs TIV case control study BC, Canada 2011 -12 • Case control, 2011 -12, control negative design • 282 participants, 84 cases and 198 controls, 136 in long term care and 132 age 85+ • Regression analysis to calculate odds ratio • Relative effectiveness lower in long term residents • a. TIV was significantly protective at around 60% (p<0. 05), TIV was not effective Influenza strategies Buynder et al Vaccine 2013; 31: 6122– 6128
Results a. TIV vs TIV case control study BC, Canada 2011 -12 Influenza strategies Buynder et al Vaccine 2013; 31: 6122– 6128
Randomised controlled trial (RCT) of a. TIV v TIV Multicentre, 2010 -11 • Randomised controlled trial, 2010– 2011 • Total of 7082 persons randomized to receive one dose of either a. TIV or TIV • Subjects ≥ 65 years old, with or without co-morbidities • USA (21 sites), Colombia (4), Panama(2), The Philippines (11) • Co-primary objectives: non-inferiority, superiority and immunogenicity 22 days after vaccination • Clinical effectiveness, reactogenicity and serious adverse events were monitored up to 1 year Influenza strategies Frey at al Vaccine 2014; 32: 5027– 5034
RCT: GMR, seroconversion and seroprotection at day 22 Multicentre, 2010 -11 Influenza strategies Frey at al Vaccine 2014; 32: 5027– 5034
RCT: GMT and seroconversion at Day 22 (95% CI) Multicentre, 2010 -11 Influenza strategies Frey at al Vaccine 2014; 32: 5027– 5034
RCT: Persistence of protection at 3 weeks, 6 months, 1 year Multicentre, 2010 -11 Influenza strategies Frey at al Vaccine 2014; 32: 5027– 5034
RCT: Results for a. TIV vs TIV Multicentre, 2010 -11 • a. TIV was non-inferior to TIV in those 65 and over • Superiority was not established on the prior criteria • a. TIV elicited significantly higher antibody responses at Day 22 against all homologous and heterologous strains, especially against A/H 3 N 2 strains, including in subjects with co-morbidities. • Improved seroconversion by 4 -13% depending on strain and match • Reactogenicity was higher in the a. TIV group, but reactions were mild to moderate and transient. Influenza strategies Frey at al Vaccine 2014; 32: 5027– 5034
JCVI advice: adjuvanted vaccine Oct 2017 • Low TIV effectiveness in 65 -74 year olds over several A(H 3 N 2) seasons, and no significant effectiveness for all types of influenza in the over 75 s • Evidence indicated adjuvanted influenza vaccines were more effective than TIV in those over 65 years of age • Under quite conservative estimates adjuvanted vaccine would be highly cost-effective in both the 65 -75 and over age groups. • Therefore, JCVI recommended a. TIV in those aged 65 years and over, with use in those 75 years and over as first priority. Influenza strategies
Strategies to minimise impact of seasonal influenza What’s new: Age based vaccine choices 1. Achieve high coverage in at-risk groups 2. Prevent transmission to vulnerable groups 3. Prophylaxis and early treatment with antivirals 4. Universal flu programme age 2 -11 y 5. Age specific vaccines of first choice: o Children 2 -17 years: LAIV 4 (6 -23 m QIV) o Adults 18 -64 years: QIV o Older adults 65 and over: a. TIV Influenza strategies
Acknowledgements • Nicola Meredith • Jane Dyson • Simon Cottrell • Malorie Perry • Ember Hilvers • Richard Lewis • Caroline Harris • Jana Zitha Influenza strategies
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