Influenza is an acute viral infection of the respiratory tract, which causes shivers, fever, headache, myalgia, arthralgia and fatigue. For healthy individuals, it can be a self-limiting disease lasting about seven days. A large number of patients (including healthcare professionals) are infected with the influenza virus but exhibit no symptoms while they are able to transmit to others the influenza virus. There is always the risk of a serious illness and this is higher among children under six months of age (they cannot be vaccinated because the influenza vaccines are not licensed as yet for this age), children under five years of age, pregnant women, the elderly (aged 65 years and over) and those with health conditions and chronic disease. The highest rates of influenza-related hospitalisations are seen in individuals over 75 years of age, as well as 74% of all influenza-associated deaths.[1]

Vaccination of high risk groups

Recognising the importance of influenza prevention through vaccination, the Department of Health has identified those at higher risk and has contracted out the responsibility to vaccinate against influenza in ‘groups at risk’ to general practitioners, pharmacists and school services [2],[3] [see Box 1]. GPs will receive a fee of £9.804 for each patient they vaccinate in the following ‘at risk groups’:

  • Age ≥65 y on 31 March 2018
  • Pregnant women
  • Patients in the ‘at risk’ groups aged 6 m to <65 years
  • Children aged 2 & 3 years
  • Locum GPs (own GP only can claim)

 

Pharmacists will receive a fee of £9.14 for vaccinating patients in the following ‘at risk groups’:

  • Age ≥65 y on 31 March 2018
  • Pregnant women
  • Patients in the ‘at risk’ groups aged 18 years to <65 years.

High risk and complications for influenza

Patients with underlying health conditions are at greater risk of complications from influenza. These can range from otitis media to bronchitis or pneumonia, but also cardiac problems, meningitis and/or encephalitis. In addition, secondary bacterial infection, usually with the pneumococcus, can occur. Patients with chronic disease may see their conditions worsen as a result of infection with the influenza viruses.

Influenza infection during pregnancy can be associated with smaller neonatal size, lower birth weight and prematurity.[6],[7] Influenza vaccination during pregnancy may reduce the likelihood of these complications,[8] provides passive immunity against influenza infection to infants,9 as well as reduces infant risk for acute lower respiratory infection.[10] It is, therefore, very important that we offer the vaccine to all pregnant patients at the beginning of the flu season, but also to women who fall pregnant during the flu season.

The impact of influenza in the elderly population is considerable. Most deaths associated with influenza occur among people 65 years and over (the older adults); they are also hospitalised more frequently than any other group of patients. The highest rates of influenza-related admissions to hospital intensive care and high dependency units are among individuals ≥ 65 years old (44%), followed by 45–64-year-olds (30%).[11] The highest rates of weekly GP consultations for influenza-like illness were seen in the ≥ 65-year old age group across England, Scotland, and Wales (but not Northern Ireland), and a significant excess all-cause mortality was noted in all four UK nations, particularly among those ≥ 65 years old.11 The primary cause of this excess mortality, particularly among the elderly, was the circulation of the influenza virus A/H3N2.[12] The same observation has been made in another 19 European regions during last year’s influenza season. Antibody responses to A/H3N2 are particularly poor in the elderly (effectiveness of 24% compared with 35% in working age adults and 43% in children).[13] This is of particular concern considering that A/H3N2 was the dominant circulating strain in the UK for four out of the last 10 years,11 and the strain that has the greatest impact in adults 65 years of age and above.[12]

bjfm oct17 influenza fig2

Lower response of the elderly to influenza vaccination

This is due to a natural deterioration of the immune system with increasing age that begins after 50 years of age. It is characterised by a decrease in the numbers of naïve B and T lymphocytes, resulting in an impaired ability to respond to challenge with new antigens. This phenomenon is called immunosenescence. The result is the reduced ability to fight infections and a lower response to conventional influenza vaccines. How can we, therefore, better protect our elderly patients from influenza and its complications?

Firstly, we need to vaccinate as many elderly (65 years old and over) as possible. Our minimum target should be the WHO’s target of 75% vaccination rate in this age. People around the elderly need to be vaccinated too (including healthcare professionals), particularly children who are the most efficient spreaders of the influenza virus and also harbour the virus for much longer, able to infect others, especially elderly relatives and family friends.

For years now we have been asking for more effective influenza vaccines in the elderly. The good news is now we do have such vaccines thanks to improved vaccine technology. The simplest method is to increase the hemagglutinin antigen content of the flu vaccine. Fluzone High-Dose® (Sanofi Pasteur, Lyon, France) was approved in the USA in 2009 for use in individuals ≥ 65 years old and is available in the USA, but not as yet in the UK. The antigenic content of this vaccine is four times that contained in the conventional influenza vaccines.

Another way to overcome immunosenescence in the 65s and over is to add an adjuvant to the flu vaccine. Adjuvant is a substance which enhances antigenspecific immune responses to vaccine antigens. The adjuvanted trivalent influenza vaccine (TIV), Fluad® (Seqirus Vaccines Ltd., Maidenhead, UK), has recently been granted a licence by the UK Government’s Medicines and Healthcare Products Regulatory Agency (MHRA) for use in the UK among adults aged 65 years and above.[14] This adjuvanted TIV (aTIV) is available for order as of August 2017 for use during the 2018– 19 influenza season. This aTIV has been shown to induce higher antibody titres against all vaccine strains (A/H3, A/H1 and B) compared with non-adjuvanted (conventional) vaccine in elderly populations.[15] In addition, the aTIV is known to induce the synthesis of cross-reactive antibodies able to provide crossprotection in subjects ≥ 60 years of age.[15] Pooled analyses demonstrated the effectiveness of the aTIV in preventing laboratory-confirmed influenza to be 60%, and the effectiveness in preventing influenza-associated hospitalisation for pneumonia to be 51%; the aTIV was also shown to be highly effective in reducing hospitalisations for acute coronary syndrome (effectiveness 87%) and cerebrovascular accidents (effectiveness 93%).[16]

The view of the JCVI

According to the (draft) minutes of 7 June 2017 meeting,[17] the JCVI states that ‘vaccine effectiveness seen in the elderly for the 2016–17 season in those aged 65 years and over was considered disappointing by the Committee. A trend for lower vaccine effectiveness against A/H3N2 in the elderly was emerging which contrasted with high A/H3N2 effectiveness in younger adults’.


One of the reasons of lower influenza vaccineeffectiveness cited by the JCVI was the phenomenon of immunosenescence in the over 65s. The JCVI had already planned to review the whole UK influenza immunisation programme in 2020, but has now agreed that ‘consideration of the over 65 year olds component of the programme should be brought forward. This was important given the data seen, and the new influenza vaccines, including an adjuvanted vaccine, would be coming onto the UK market’.

Conclusion

According to recently released data, in the UK in 2015, influenza and pneumonia were the fourth and sixth leading causes of death among women and men, respectively.[18] These are deaths we can prevent to a large extent.


The ‘groups at risk’, as defined by the Department of Health, are patients that are most vulnerable to influenza infection and its devastating complications. Although the UK influenza vaccination rates are the best in Europe, we could and need to do more in order to reduce deterioration of chronic disease, hospitalisations, visits to general practitioners, and also deaths among the most vulnerable. The UK has one of the best and most effective influenza vaccination programmes as well as a committed to prevention by vaccination Department of Health. Our vaccination rate can be much higher than what currently is and further benefits from vaccination are possible. Vaccine technology is now allowing us to overcome natural phenomena, particularly immunosenescence in the elderly.

References

1 Matias G, Taylor RJ, Haguinet F, Schuck-Paim C, Lustig RL, Fleming DM. BMC Public Health 2016;16:481
2 The Flu Plan: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/600532/annual_flu_plan_2017t2018.pdf [Accessed September 2017]
3 The Green Book: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/456568/2904394_Green_Book_Chapter_19_v10_0.pdf [Accessed September2017]
4 https://www.england.nhs.uk/wp-content/uploads/2017/08/17-18-service-specification-seasonal-flu.pdf [Accessed September 2017]
5 http://psnc.org.uk/services-commissioning/advanced-services/flu-vaccination-service/ [Accessed September 2017]
6 Pierce M, Kurinczuk JJ, Spark P et al. (2011) BMJ. 342:d3214.
7 McNeil SA, Dodds LA, Fell DB et al. (2011) Am J Obstet Gynecol. 204:(6 Suppl 1) S54-7.
8 Omer SB, Goodman D, Steinhoff MC et al. (2011) PLoS Med. 8:(5) e1000441
9 Benowitz I, Esposito DB, Gracey KD et al. (2010). Clin Infect Dis. 51:1355-61
10 http://www.infectiousdiseaseadvisor.com/influenza/infantacute-lower-respiratory-infections-maternal-influenza-vaccine/article/683712/ [Accessed September 2017]
11 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/613493/Surveillance_of_influenza_and_other_respiratory_viruses_in_the_UK_2016_to_2017.pdf [Accessed July 2017]
12 Vestergaard LS, Nielsen J, Krause TG, et al. European communicable disease bulletin 2017;22
13 Belongia EA, Simpson MD, King JP, et al. The Lancet infectious diseases 2016;16:942-51
14 Medicines and Healthcare Products Regulatory Agency (UK). Summary of Product Characteristics, Fluad Influenza Vaccine (2016 – 17 Season). 2017: http://www.mhra.gov.uk/ spc-pil/index.htm?prod Name= FLUAD%20SUSPENSION%20FOR%20INJECTION%20IN%20PRE-FILLED%20SYRINGE&subsName=&pageID=ThirdLevel&searchTerm=fluad#retainDisplay [Accessed August 2017]
15 Camilloni B, Basileo M, Valente S, Nunzi E, Iorio AM. Human vaccines & immunotherapeutics 2015;11:553-63
16 Puig-Barbera J, Diez-Domingo J, Varea AB, et al. Vaccine 2007;25:7313-21
17 https://app.box.com/s/iddfb4ppwkmtjusir2tc/file/198733240440 [Accessed September 2017]
18 PHE. Public Health England. Research and analysis. Chapter
2: major causes of death and how they have changed. Published 13 July 2017. Available at: https://www.gov.uk/government/publications/health-profile-for-england/chapter-2-major-causes-of-death-and-how-they-have-changed [Accessed 13 July 2017].


Dr George Kassianos, FRCGP, FBIHS, FESC, FBGTHA, FHEA, FAcadMEd, FFTM RCPS Glasgow President British Global & Travel Health Association, Chair of RAISE Pan-European Committee on Influenza, RCGP National Immunisation Lead