1. Influenza Disease and Available Vaccines
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2. Colourised TEM of influenza A
Influenza – the virus
Single stranded helically shaped RNA virus of the orthomyxovirus family
Four basic virus types: A, B, C and D
Type A
Moderate to severe illness in all age groups
Humans and other animals
Type B
Moderate disease
Humans only
Type C
Rarely reported in humans
No epidemics
Type D
Primarily affects cattle
Not known to cause illness in humans
Colourised TEM of influenza A
Copyright: public domain Courtesy of CDC/Dr J A MurphySource: phil.cdc.gov
Centres for Disease Control and Prevention. Accessed April 2018

3. Virus types Type A influenza virus Type B influenza virus
Subtypes determined by surface glycoproteins
18 H subtypes & 11 N subtypes
Type B influenza virus
More stable than influenza A
Not divided into subtypes, however two genetically/antigenically distinct lineages exist
Type C influenza virus
Most cases mild or sub-clinical
Has not been associated with epidemic disease
H = Haemagglutinin
N = Neuraminidase
Centres for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink book). 13th ed. 2015; Chapter 12 – Influenza
van de Sandt CE, et al. Future Microbiol 2015;10(9):

4. Influenza – nomenclature
Location of laboratory where first isolated
Year identified
A / Singapore / 6 / 86 (H1N1)
Influenza type
Laboratory number of the strain
Subtype

5. Unpredictability of the circulating flu viruses
Changes in the surface antigens (H and N) result in the flu virus constantly adapting and evolving
Antigenic SHIFT: when two or more different strains combine (genetic recombination or reassortment). This abrupt major change results in a new subtype, potentially leading to a widespread epidemic or pandemic (due to low or no previous immunity in population)
Antigenic DRIFT: minor changes (natural ‘point’ mutations) in the genes of flu viruses that occur gradually over time
Because of the changing nature of flu viruses, the World Health Organization (WHO) monitors their epidemiology throughout the world
Public Health England. National flu programme training slide set for healthcare professionals 2016/17. July 2016
Plotkin, S.A et al. Vaccines. (6th edition). Chapter 17 – Inactivated influenza vaccines. Elsevier Saunders, 2013

6. Influenza virus – History
1933 – influenza virus was first isolated 1940 – second strain isolated, “influenza B”, first strain named “influenza A” (later became known as H1N1) 1947 – antigenic drift of surface proteins discovered 1958 – new influenza A strain identified (H2N2) 1968 – new influenza A strain identified (H3N2) 1978 – two A and one B strain (H1N1 reappeared and co-circulated with H3N2) 1980s – B/Victoria dominant B strain 1990s – emergence of B/Yamagata: dominant next 10 years 2002 – B/Victoria reappeared and co-circulated with B/Yamagata: two B strains identified
Key point:
Discovery of antigenic shift and drift ‘ability’ of flu virus, due to vaccination failures when presence of new viruses were identified
Since 2002 both lineages have co-circulated in most seasons in both hemispheres
Hannoun C. Expert Rev Vaccines 2013;12(9):

7. Transmission
By droplets, aerosol, or through direct contact with respiratory secretions (e.g. on surfaces) of someone with the infection
Spreads rapidly, especially in closed communities
Adults can transmit flu from the day before symptom onset to approx. 5 days after symptoms begin
Children can transmit flu to others for 10 days or more
Public Health England. Immunisation against infectious disease (The Green Book): Influenza – chapter 19
Centres for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink book). 13th ed. 2015; Chapter 12 – Influenza

8. Complications
Secondary bacterial pneumonia (usually associated with Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae), bronchitis, otitis media in children
Meningitis, encephalitis or meningoencephalitis more unusual
Other infrequent/rare complications:
Primary viral pneumonia
Reye’s syndrome (primarily in children infected with influenza B)
Myocarditis
Pericarditis
Sepsis
Death
Reye’s syndrome = Very rare but severe condition that causes swelling of the liver and brain. If not treated promptly, may result in permanent brain injury or death. Mainly affects children and young adults under 20 years of age. The exact cause of Reye's syndrome is unknown, but most cases have occurred in children and young adults recovering from a viral infection – typically, but not exclusively, flu or chickenpox – and in most of these cases they had taken aspirin to treat their symptoms (NHS Choices, Sep 2015).
Public Health England. Immunisation against infectious disease (The Green Book): Influenza – chapter 19
Plotkin, S.A et al. Vaccines. (6th edition). Chapter 17 – Inactivated influenza vaccines. Elsevier Saunders, 2013

9. Epidemiology

10. over 1 million (depending on ref source)
Pandemics
4 subtypes have caused human pandemics
2009 – “Swine Flu”
18,500
H1N1
1968 – “Hong Kong Flu”
1 – 3 million
H3N2
1957 – “Asian Flu”
over 1 million (depending on ref source)
H2N2
1918 – “Spanish Flu”
40 – 50 million

11. Global flu surveillance – WHO
Sentinel Doctors
(local GPs in case of UK)
National Influenza Centres
(national laboratories >140 worldwide)
Collaborating Reference Centres for
Research against influenza
(Melbourne, Beijing, Tokyo, London, Atlanta & Memphis)
World Health Organization
(WHO – Geneva)
Global Influenza Surveillance and Response System (GISRS)

12. Sources on circulating influenza strains:
UK flu surveillance
Surveillance collated by Respiratory Diseases Department (RDD) of Public Health England’s (PHE) National Infection Service (NIS)
Collaboration with HPS, PHW and N Ire’s PHA
Sources on circulating influenza strains:
Primary Care
GP consultations for ILI through RCGP scheme
Secondary Care
UK Severe Influenza Surveillance Systems (USISS)
Community syndromic surveillance (GP out of hours, emergency, NHS 111 calls)
Outbreak reporting (hospitals, care homes, schools)
Internet-based surveillance (Flu survey)
Ref: PHE Surveillance of Influenza and other respiratory viruses in the United Kingdom: Winter 2015 to May PHE ref:

13. PHE Influenza Surveillance graphs (2018) accessed at https://assets

14. 2016/17 season
PHE Influenza Surveillance graphs (2017). Accessed at:

15. 2017/18 Season
PHE Influenza Surveillance graphs (2018) accessed at

16. PHE Respiratory Virus circulation (2018) https://assets. publishing

17. Influenza vaccines

18. Vaccine composition
Each year, influenza vaccines are manufactured to include the virus strains recommended by the World Health Organization (WHO) The WHO recommends the A and B strains to be included in trivalent influenza vaccines (TIVs) and quadrivalent influenza vaccines (QIVs)
World Health Organization. Recommended composition of influenza virus vaccines for use in the northern hemisphere influenza season Accessed in April 2018

19. Vaccine production Quality control OCTOBER–JANUARY FEBRUARY 1 2 3 4 5
WHO issues composition of flu vaccines
Vaccination clinics 1 2 3 4 5 6 7 8
SEPTEMBER
MARCH
Deliveries
Grow flu virus
Quality control
AUGUST
APRIL / MAY
Fill vaccine and batch release
Public Health England flu letter
JULY
MAY
Run clinical trials and obtain licence
Formulate vaccine

20. QIVs include both B strains, as well as the 2 chosen A strains
Vaccine composition
TIVs contain 2 subtypes of influenza A strains together with just 1 of the 2 potential circulating B strains ( )
TIV: + + or
A/H1N1
A/H3N2
B/Yamagata
B/Victoria
QIVs include both B strains, as well as the 2 chosen A strains
QIV: + + +
A/H1N1
A/H3N2
B/Yamagata
B/Victoria
World Health Organization. Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season Accessed in April 2017
03/2018

21. B strain mismatches took place during four out of ten seasons
Flu season
TIV vaccine B lineage
Predominant circulating B lineage in the UK
TIV match or mismatch?
2006 – 07
Victoria
Yamagata
Mismatch
2007 – 08
2008 – 09
2009 – 10
Match
2010 – 11
2011 – 12
2012 – 13
2013 – 14
2014 – 15
2015 – 16
A mismatch of the B strain took place during 3 consecutive seasons in the UK from 2006 to 20091
The 2015 – 16 flu season was a mismatch between vaccine and the predominantly circulating B lineage2
1. Pockett R, et al. Plos One 2015;10:1019; 2. Public Health England. Surveillance of influenza and other respiratory viruses in the United Kingdom: Winter 2012/13, Winter 2013/14, Winter 2014/15 and Winter 2015/16

22. Quadrivalent influenza vaccines (QIVs)
“QIVs are considered the best option for 18–65 at-risk groups for the 2018/ flu season”1
“Quadrivalent vaccines include a 2nd influenza B virus in addition to the viruses in trivalent vaccines, and are expected to provide wider protection against influenza B virus infections”2
“The use of quadrivalent influenza vaccines containing a B strain from each lineage is expected to improve the matching of the vaccine in the future”1
Joint Committee on Vaccination and Immunisation (JCVI)
World Health Organization (WHO)
Department of Health
(The Green Book)
1. Public Health England. Immunisation against infectious disease (The Green Book) Influenza: Chapter 19. Accessed April World Health Organization. Influenza Fact Sheet. January Available at: Accessed April 2018

23. Influenza Vaccination Programme

24. 2018/19 flu season vaccination recommendations
For the 2018/19 flu season, the following populations are eligible for flu vaccination:
All children aged two to nine (but not ten years or older) on 31 August 2018
All primary school-aged children in former primary school pilot areas
Those aged six months to under 65 years in clinical risk groups
Pregnant women
Those aged 65 years and over
Those in long-stay residential care homes
Carers
The National flu immunisation programme 2018/19. Available at: Accessed April 2018.

25. Under 65 clinical risk groups
Clinical risk groups who should be offered influenza immunisation (provided they are over the age of six months)
Clinical risk categories: Recommended to receive annual influenza vaccination
Chronic respiratory disease
Chronic heart disease
Chronic kidney disease
Chronic liver disease
Chronic neurological disease
Diabetes
Immunosuppression
Asplenia or dysfunction of the spleen
Pregnant women
Morbid obesity: adults with a BMI ≥40 kg/m2
Adapted from: Public Health England. Immunisation against infectious disease (Green Book) , Chapter 19: Influenza. Accessed April 2018

26. Vaccination of all pregnant women
Recommended to receive a flu vaccine irrespective of their stage of pregnancy
Pregnant women are at increased risk of complications if they contract flu
Flu during pregnancy may be associated with premature birth and smaller birth size and weight
Flu vaccination during pregnancy helps to provide protection against flu to infants during the first few months of life
Photograph courtesy of morgue file
Accessed February 2016
The National flu immunisation programme 2018/19
Available at: Accessed April 2018

27. Vaccination of health and social care workers
Immunisation should be offered by NHS organisations to all employees involved in delivering care1
As part of the organisation’s Infection Prevention Strategy
Have a duty of care to protect their patients and colleagues from infection
Reduce transmission of influenza viruses in health and social care premises
Contribute to the protection of individuals who may have a suboptimal response to their own immunisations
Avoid disruption to services providing care
Help protect family and friends
For more information please refer to the Green Book, Chapter 19, Influenza
1. Public Health England. The National flu immunisation programme 2017/18. Available at: Last accessed April 2017

28. Seasonal flu vaccine uptake (GP) 2017/18 – provisional data on GP registered patients
Provisional end of January 2018 cumulative uptake data for England on influenza vaccinations given from 1 September 2017 to 31 January 2018
Adapted from: Public Health England. Seasonal influenza vaccine uptake amongst GP Patients in England. Provisional monthly data for 1 September 2017 to 31 January

29. Influenza vaccines for the 2018/19 season

30. 2018/19 flu season vaccination recommendations
Latest clinical evidence from the JCVI and PHE offers guidance to ensure use of the most effective vaccines for certain populations:1
Population
Vaccine recommendation
18–under 65s at-risk:
≥65:
Quadrivalent vaccines (QIVs) + + +
QIV:
A/H1N1
A/H3N2
B/Yamagata
B/Victoria
Adjuvanted trivalent vaccine (aTIV) + +
TIV:
A/H1N1
A/H3N2
B/Victoria
JCVI: Joint Committee on Vaccination and Immunisation. PHE: Public Health England.
1. Vaccine ordering for influenza season letter to GPs and community pharmacies. February Available at: Accessed April 2018.

31. Reasons for selecting QIVs/aTIV influenza vaccines
Reasons for selecting vaccines in target populations
QIVs (recommended in 18–under 65 at-risk)
aTIV (recommended in ≥65s)
QIVs cover the two main B lineages , thereby helping to extend the breadth of protection against influenza B (compared to one B strain in TIVs)
Following PHE modelling, on average, use of QIVs over TIVs is likely to lead to reduced activity in terms of GP consultations and hospitalisations due to flu
Data indicates the aTIV has higher immunogenicity and effectiveness than non-adjuvanted vaccines in the elderly
Given low flu vaccine effectiveness seen in the elderly, the JVCI agreed that use of aTIV in ≥65s would be more effective, and more cost-effective, than the non-adjuvanted vaccines
1. Summary of data to support the choice of influenza vaccination for adults in primary care. January Available at: Accessed April 2018.

32. 2017/2018 season: influenza in England
In season a higher rate of circulating type B influenza than type A influenza1
Influenza confirmed ICU admissions by age and influenza subtype, since October 2017
<1
Number
Age group (years)
1–4
5–14
15–44
45–64
65+
200
400
600
800
1000
1200
A(H1N1)pdm09
A(H3N2)
A unknown subtype B
A large proportion of influenza- confirmed ICU admissions is caused by type B influenza1
Since the beginning of October 2017, the highest rates of type B influenza is observed in 45–64 and 65+ year olds1
Influenza vaccination uptake in England (up to the end of January):
65+ years: 72.4%
<65 at-risk: 48.7%
ICU: intensive care unit.
1. Public Health England. Weekly National Influenza Report. Week 11. Available at: Accessed April 2018.

33. Vaccination uptake targets for the 2018/19 flu season
Eligible group
Uptake ambition
<65 at-risk
At least 55% in all clinical risk groups
Ultimately aim to achieve at least 75%
≥65s
75% (reflecting the WHO target for this group)
Providers should actively invite 100% of eligible individuals to ensure uptake is as high as possible
The National flu immunisation programme 2018/19. Available at: Accessed April 2018.

34. ?
Thank you
Any questions