Déjà flu: can science help the NHS cope with the annual burden of respiratory infections?

Last winter’s flu season was widely covered as having put huge pressure on the NHS, with reports the NHS is being thrown into ‘crisis’. What went wrong? And how can the NHS be supported in the future?

At the Microbiology Society’s Annual Conference 2018, Dr Richard Pebody from Public Health England and Professor Derek Smith from Cambridge University discussed the challenges in predicting which flu strain will spread, and how we can better prepare for the upcoming flu season. During their talk, Déjà flu: can science help the NHS cope with the annual burden of respiratory infections? the speakers explained why the 2017/18 flu season was so ‘tough’, and what the future of flu control might look like.

The 2017/18 Flu Season:

Flu activity for the 2017/18 season started in December. Outbreaks of respiratory illnesses rose rapidly, particularly in care homes. During this period, there was also a steep rise in GP consultations for influenza-like illness. Burden did not only fall on primary care services, however. The 2017/18 flu season had the highest case of flu-confirmed hospitalisations since 2010/11, with older age groups being the worst affected.

What caused the respiratory infections?

  • ‘Aussie flu’: This is a strain of Influenza A, subtype H3N2. This was the dominant flu subtype in both the 2017/18 and 2016/17 seasons.
  • ‘Japanese flu’: This strain of Influenza B, from the Yamagata lineage also caused disease in the UK. This winter was colder and longer than usual, which meant the virus could circulate and cause disease for longer.
  • Respiratory syncytial virus (RSV): This virus usually affects children, but also causes disease in the elderly. RSV outbreaks occur each winter, mainly during December ‘like clockwork’, according to Richard Pebody.
  • Pneumonia: Caused by Streptococcus pneumoniae, usually occurs as a secondary infection to influenza.

Preventing flu:

The circulating flu virus changes each year. Predicting the flu type and strain, and when the flu season is going to start is challenging, and the considerable variation means that healthcare systems struggle to prepare.

In order to evade the immune response, the surface proteins of viruses frequently mutate to avoid recognition – a process known as antigenic evolution. These proteins are targeted by the immune system after infection or vaccination. Since the proteins mutate so frequently, vaccines may only be effective for a short window of time.

The vaccine developed for the 2017/18 season failed to match the viral subclades on the circulating H3N2 strain. A subclade is a sequence of nucleic acids and are often targeted by vaccines.  Some 2017/18 vaccines did protect against the Influenza B, Yamagata lineage, but it was only provided by quadrivalent vaccines, which protect against four types of flu, two A types and two B types, and are not usually given to the elderly.

 

How are flu vaccines chosen?

 

Despite a promising vaccine uptake in target groups, Richard Pebody said protection against H5N2 in older adults is ‘less optimal’, particularly when compared to the 50% protection seen after vaccination of children and younger adults.

Vaccine uptake in target groups:

Target group 2017 vaccine uptake
The elderly (> 65 years old) 73%
At-risk adults 49%
Healthcare workers 68%
Pregnant women 47%

 


What does the future look like?

Segmented strategy:

PHE is developing a new strategy for vaccine administration in the UK. The plan involves using different vaccines for different age groups:

  • Children aged two to 16 years will be vaccinated with a live-attenuated vaccine. The vaccine will be administered universally, and the resulting immunity will not only directly protect the children but is anticipated to indirectly protect other members of society by reducing the circulation of the virus. The vaccine has only been recently licenced, but initial evaluations of the programme have been ‘encouraging’ said Richard Pebody.
  • Adults will be vaccinated with quadrivalent vaccines. These protect against four circulating influenza strains, two of which are Type B. Studies have shown that quadrivalent vaccines are more cost-effective than trivalent vaccines, which protect against three types of flu, two A types and one B type..
  • Adults over 65 years of age will be administered a newly-licenced adjuvanted vaccine. Adjuvanted flu vaccines have been used widely outside of the UK, particularly in North America, and are intended to provide increased effectiveness when compared to the current vaccines.

‘Flu vaccine uptake continues to increase in key target age groups, and it is really important to continue to build on those successes by implementing these different interventions.’ – Richard Pebody

Prediction models:

Research teams in the US and the UK are working on developing models which make short-term predictions of virus activity. The models could be able to anticipate when peak virus activity is expected and how significant this activity might be from 1-4 weeks in advance. Models like this would be useful in short-term planning for health care providers, and hopefully enable services to better prepare for periods of high burden.

Future vaccines:

Derek Smith discussed the work being done by himself and his research team, where models are being developed to predict where the mutations that change the virus will take place. ‘The evolution might be more predictable than one might imagine’, he said.

If the right virus proteins are chosen for the vaccine, it is likely better protection against the virus. A vaccine is being designed which researchers hope will predict how the virus will mutate and ‘get ahead’ of the evolution of flu. Smith hopes that the vaccine will be moving into Phase 2 clinical trials in two to three years.

In addition to the above developments, Richard Pebody said there are also new vaccines for RSV on the horizon: ‘The hope is that they will provide better opportunities to further reduce the annual burden and impact of these important infections, and thus, hopefully help the NHS cope each winter.’

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