Sarah James is currently working with the PHG Foundation as a policy analyst, alongside her role as an influenza researcher at the Centre for Pathogen Evolution, University of Cambridge.

At the end of February 2017,  over 30 scientists gathered at the World Health Organization (WHO) headquarters in Geneva for a biannual meeting to take a decision that affects more than 100 million people worldwide – which virus strains should be used to make the annual influenza vaccine? I attended as a representative of the WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Disease, University of Cambridge.

Influenza is important

Influenza is a serious global health problem, causing 250,000-500,000 deaths and three to five million cases of severe illness each year. For some people it is a mild illness, but it can be more dangerous, especially to those with underlying health problems such as asthma and other chronic lung diseases. There are four types of influenza viruses currently circulating in people, A/H3N2, A/H1N1, B/Victoria and B/Yamagata. Influenza is a seasonal illness and this winter the main circulating virus has been A/H3N2. Our chief weapon against influenza is vaccinat ion, which in the UK is recommended to be offered in the autumn to young children, pregnant women, the elderly and other high risk groups

Evolution of influenza – a moving target

Early influenza vaccines, introduced in the 1940s, worked excellently. A few years later, they were practically useless. Influenza had pulled a trick that other vaccine-preventable viral illnesses, such as measles, mumps and rubella, are not able to. The influenza virus had mutated to escape being recognised by the immune system. Constant surveillance of circulating influenza viruses is essential to determine whether a virus is still recognised by the immune system of vaccinated people. If it is not, then a new vaccine is needed. 

The WHO has issued vaccine recommendations since 1973, based on a biannual consultation meeting with influenza experts. In that time, the A/H3N2 component of the vaccine has been changed 29 times.

Sequencing and Sharing

A global network of more than 150 laboratories in over 100 different countries collects and analyses influenza viruses. Experiments on blood samples taken from infected animals and vaccinated people have been the main data source for identifying which viruses are in circulation, with experts also using information on geographic spread, number of cases and clinical outcome. This information is now supported by genetic sequencing which can identify mutations responsible for enabling a virus to evade the immune system, as well revealing how different influenza viruses travel around the world. 

The combined results are uploaded to a database, the Global Initiative on Sharing All Influenza Data. Mathematical modellers use the sequence data to predict which strains of influenza are more likely to dominate in the next influenza season and to prioritise experimental work.

This work is only made possible by the many laboratories in the WHO Global Influenza Surveillance and Response System (GRSIS) who are sharing viruses and genetic sequences in the influenza sequence database, EpiFlu™. Unlike other genetic sequence databases where anyone can download the data to use as they wish, users of EpiFlu™ must register to use the database, are not allowed to republish the data and must acknowledge the submitting laboratory in any publications resulting from use of the data. These restrictions are encouraging scientists to put the influenza sequences in the database so that others can benefit.

The decision

The biannual meeting was an intense but enjoyable three days, integrating the diverse evidence from the different laboratories. This time the vaccine recommendation was the same as in September 2016 for all four types of influenza. But influenza will not stop evolving, and work to characterise the circulating viruses must go on until researchers are able to develop a vaccine that works long term against all types of influenza.

Influenza as a model

Governments contribute substantial funding to WHO Collaborating Centres and the National Influenza Centres. A key factor in the success of these collaborations is leadership from the WHO and the Collaborating Centre Directors, whose early recognition of the value of genetic sequencing means it is now embedded into routine surveillance. Cooperation is also essential to controlling infectious diseases in an interconnected world and, while academics and scientists are often caricatured as secretive, disorganised and obsessed with self-promotion, the WHO GISRS is demonstrating they can and do work together to meet the challenges of seasonal influenza and rarer, but potentially devastating, pandemics.

The benefits and challenges of genome sequencing of infectious disease agents are outlined in the PHG report, Pathogen Genomics into Practice . Sequencing is a highly sensitive method for determining how different strains are related, which adds valuable information in the investigation of infectious disease outbreaks. Both of these approaches are being explored by the National Infection Service of Public Health England. Although there are implementation hurdles, infectious disease genomics has the potential to transform the management of infectious diseases, and influenza surveillance is a shining example of this on a global scale.

Sarah provides research support for a variety of projects at PHG Foundation, working on the clinical applications of long read sequencing, and the infectious diseases genomics programme.

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