Introduction
Vaccination
JCVI minutes
Public Health England
NHS England update
Wales update
Who should be vaccinated?
Conclusion
References

 

 

Introduction

Seasonal influenza causes a substantial annual health and economic burden across the UK and, according to new figures released recently by Public Health England (PHE), early January has seen flu hospital admission levels rise by up to 50%. GPs have also seen a 78% increase in consultation rates for flu-like illness.1

The influenza-attributable mortality burden is concentrated in the elderly population aged over 65 years.2 One study found that there was an annual average of over 300,000 admissions for acute respiratory illness among those without comorbidities, what we would normally consider as healthy individuals, and almost 520,000 among those in a clinical risk group; the majority of the admissions and the highest case fatality rates were in over 65 year olds.2

However, this mortality burden in the elderly is not uniformly distributed, and individuals over 75 years are on average seven times more likely to die from influenza than a 65-74 year old.3 According to PHE, there has been a 65% increase in the flu intensive care admission rates at the beginning of January and it is likely the majority will be in the older age group.

The main strains currently circulating continue to be flu A(H3N2), A(H1N1) and Flu B.

 

Vaccination

Annual influenza vaccination is the best available method of protection against influenza, and is the primary strategy for disease control and prevention. Available vaccines today are trivalent, which contain the three viral strains that cause seasonal epidemics—two A viruses (A/H1N1 and A/H3N2) and one B virus, or quadrivalent, which in addition contains a second B lineage.

There is increasing evidence of poor performance of currently used inactivated (injectable) standard influenza vaccines in older people (65 years and over). A meta-analysis of data between 2004 and 2015 did not show any significant efficacy for the inactivated influenza vaccine in the elderly against the A(H3N2) influenza virus.4 This influenza sub-type is associated with significant impact in older people typically resulting in excess mortality and causing outbreaks in often highly vaccinated residents in care homes.

PHE have also conducted an age stratified analysis of pooled primary care data since 2010/11. This showed significant vaccine effectiveness in the 65-74 age group for all influenza, for A(H1N1) pdm09,and for influenza B, but no evidence of significant protection against A(H3N2). Above the age of 75 years, pooled estimates were unable to demonstrate any significant effectiveness across all seasons against influenza. Therefore, data from PHE demonstrate no significant clinical effectiveness of the currently available inactivated influenza vaccines in our elderly population for the influenza virus strain A(H3N2).

In response to the limited effectiveness of standard vaccines in older people, some pharmaceutical companies have been developing vaccines that lead to a better immune response in this group. Sanofi Pasteur have developed an influenza vaccine that uses four times the amount of antigen for each strain (60mcgs instead of 15mcgs) used in our current flu vaccines. This vaccine is not as yet available to order in the UK. On the other hand, an adjuvanted trivalent inactivated influenza vaccine (aTIV) Fluad® is now licensed in the UK for use in those aged 65 years and older. The aTIV has been licensed in some countries in Europe since 1997 and in the USA since 2015.

 

BOX 1: GROUPS RECOMMENDED TO RECEIVE VACCINATION UNDER THE UK NATIONAL HEALTH SERVICE INFLUENZA VACCINATION PROGRAMME FOR THE 2017-18 INFLUENZA SEASON
  • People aged 65 years or over (including those becoming age 65 years by 31 March 2018)
  • People aged from 6 months to <65 years of age with a serious medical condition, such as:
    • Chronic (long-term) respiratory disease, such a severe asthma requiring inhaled steroids or with previous exacerbations requiring hospital admissions, COPD, emphysema, bronchiectasis, cystic fibrosis, interstitial lung disease, pneumoconiosis, bronchopulmonary dysplasia
    • Chronic heart disease including congenital heart disease, heart failure, hypertension but only if with cardiac complications such as left ventricular hypertrophy
    • Chronic kidney disease at stage 3, 4 or 5, nephrotic syndrome, kidney transplantation
    • Chronic liver disease—cirrhosis, biliary atresia, chronic hepatitis
    • Chronic neurological disease, including learning disability, stroke, TIA, post-polio syndrome, multiple sclerosis, hereditary and degenerative disease of the nervous system or muscles, severe neurological disability
    • Diabetes type 1 & type 2 whether on medication or diet controlled
    • Splenic dysfunction, includes asplenia homozygous sickle cell disease, coeliac disease as it may lead to hyposplenism
    • Weakened immune system due to disease, treatment or medical intervention such as chemotherapy, bone marrow transplant, multiple myeloma, genetic disorder affecting the immune system (eg. complement disorders), HIV infection at all stages, individuals treated or likely to be treated with systemic steroids for more than a month at a dose equivalent to prednisolone 20mg or more per day (if a child under 20kg, a dose of 1mg or more per kg body weight per day).
    • Morbid obesity (BMI of >_ 40kg/m2)
  • All pregnant women (at any stage of pregnancy), including those who become pregnant during the flu season
  • All those 2 and 3 years of age (but not over 4 years) on 31 August 2017 (to be vaccinated by GP Practices)
  • All children in reception class and of school years 1, 2, 3, and 4 (aged 4-8 years old—to be vaccinated by the school services)
  • Primary school aged children (5-11 years old) in former primary school pilot areas
  • People living in long-stay residential care homes or other long-stay care facilities
  • Carers—who are in receipt of a carer’s allowance, or those who are the primary carer of an elderly or disabled person whose welfare may be at risk if the carer falls ill
  • People living with immunocompromised individuals will be taken into consideration
  • Locum General Practitioners (vaccinated by their registered medical practice)
  • Care home staff can be vaccinated on the NHS

 

 

Published data indicates that the adjuvanted influenza vaccine has higher vaccine immunogenicity and higher effectiveness than non-adjuvanted vaccines in the elderly.5

In practice, the aTIV induces a higher level of antibodies for all three flu virus strains, that last longer, therefore, overcoming to a good degree the effects of immunosenescence (lower response to the conventional flu vaccine and shorter lasting antibodies against the flu strains in the vaccine) in the over 65 years group.

 

JCVI minutes

Given the low influenza vaccine effectiveness seen in those aged 65 years and over in seasons dominated by A(H3N2), the Joint Committee on Vaccination and Immunisation (JCVI)—which advises UK health departments on vaccination policies—agreed in their October 2017 meeting (draft minutes at the time of writing) that use of aTIV in those aged 65 years and over would be both more effective and cost-effective than the non-adjuvanted (conventional inactivated) vaccines currently in use.6

It has been estimated that between 7,000 and 25,000 deaths were associated with influenza in the winter periods 1999-2009, with the mortality burden highest among the over 75 age group.7

Therefore, the priority for adjuvanted vaccine should be for those aged 75 years and above as this age group appear to derive hardly any benefit from the standard vaccine.8

The vaccine would, however, also be effective and cost-effective in 65-74-year olds.6 Given the evidence about the low effectiveness of current inactivated flu vaccines in our elderly population, the trivalent adjuvanted vaccine (aTIV) is a more appropriate choice than standard flu vaccines for older people.

 

Public Health England

Public Health England has now produced a summary of data to support the choice of influenza vaccination for adults in primary care.9

Based on the existing evidence, and in the context of the UK programme, PHE analysis strongly supports the preferential use of adjuvanted trivalent vaccine in older people. Based on current list prices for adjuvanted and standard vaccines, it notes that such a programme is likely to be highly cost effective. It added that, as advised by JCVI, the priority for 2018/19 should be those over 75 years of age, as this group are likely to derive very limited benefit from the existing programme (the currently used inactivated flu vaccines).

 

NHS England update

NHS England also issued an update on the use of adjuvanted trivalent flu vaccine for the 2018-19 flu season at the end of December 2017.8

It said that the JCVI has accordingly advised that the use of the adjuvanted trivalent flu vaccine (Fluad®) should be a priority for those aged 75 years and over, given that the non-adjuvanted inactivated vaccine has showed no significant effectiveness in this group over recent seasons, and the adjuvanted trivalent flu vaccine is, therefore, currently considered to be the only licensed cost-effective option for this group.

 

Wales update

In November, the Chief Medical Officer for Wales sent a letter for action by GPs pharmacists and chief executives of health boards and trusts also highlighting updated advice from the JCVI on the cost effectiveness of particular flu vaccines.10

It said that:

  • Quadrivalent vaccine is cost effective in those aged 6 months to 64 years in clinical risk groups.
  • The adjuvanted trivalent vaccine is cost effective when administered to those aged 65 to 74 years.
  • The adjuvanted trivalent vaccine is the only clinically effective and cost-effective option for those aged over 75 years.

The Welsh CMO’s letter added that practices will wish to consider more than one supplier for injectable vaccine, where possible. This is in order to be able to meet the needs of their practice population, particularly in cases where a particular vaccine manufacturer is unable to supply vaccine.

 

Who should be vaccinated?

GPs (and pharmacists—can only vaccinate individuals aged 18 years and over) aim to increase influenza vaccine uptake among patients eligible for NHS influenza vaccination each year and order sufficient vaccine to protect:

  • At least 75% of patients aged 65 years and older
  • At least 55% of patients in the clinical at risk groups (with chronic disease) aged 6 months to 64 years
  • All pregnant women
  • Children aged 2 and 3 years (aged 4 to 8 years are vaccinated at school)
  • Patients in long-stay residential homes
  • Carers of disable or elderly people
  • Care home staff
  • Locum GPs (their own registered GP).

 

Conclusion

As we prepare for the next influenza season by ordering our vaccines in advance of the start of influenza vaccine production in February, we are in a very fortunate situation to have already received advice from the JCVI, PHE, NHS England and the Welsh Chief Medical Officer as regards to the choice of vaccine we should be using for our elderly population.

The advantages are considerable. If we can follow their advice, we will be able to offer our elderly a more effective influenza vaccination. By improving their vaccine-induced immunity, we should see less elderly deteriorating at home, less admissions to hospitals, less demands on our hospitals, social services and primary care services, less demand on medication, and less deaths among our elderly patients. We now have a clear choice.

 

Dr George Kassianos, GP, National Immunisation Lead, Royal College of General Practitioners, Chair RAISE Pan-European Committee on Influenza, President British Global & Travel Health Association

Conflict of interest: Received honoraria for lectures and advisory boards in the last 12 months from Sanofi Pasteur, MSD, Pfizer, AstraZeneca, Seqirus, Valneva

 

References

1. https://www.gov.uk/government/news/uk-flu-levels-continueto-increase-according-to-phe-statistics

2. Cromer D, van Hoek AJ, Jit, M, et al. The burden of influenza in England by age and clinical risk group: a statistical analysis to inform vaccine policy. Journal of Infection 2014; 68(4), 363–71

3. Public Health England analysis (unpublished, in preparation)

4. Bellongia E, Simpson M. King J, et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet 2016; 16 (8): 942–51

5. Van Buynder PG, Konrad S, Van Buynder JL, et al. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 2013; 31(51): 6122–8

6. https://www.gov.uk/government/groups/joint-committee-onvaccination-and-immunisation#minutes

7. Hardelid P, Pebody R, Andrews N. Mortality caused by influenza and respiratory syncytial virus by age group. Influenza Other Respir Viruses 2013; 7(1): 35-45

8. NHS England S7a Public Health Commissioning Team. Update on use of adjuvanted trivalent flu vaccine for 2018-19 flu season. Leeds: NHS England, 2017 Publication Gateway number: 07529 https://www.england.nhs.uk/publication/trivalent-flu-vaccine-2018-19/].

9. https://www.devoncepn.co.uk/images/PHE_-_Summary_of_data_to_support_the_choice_of_influenza_vaccination_ for_.pdf]

10. http://gov.wales/docs/dhss/publications/171129whc052en.pdf