̽��ֱ�� of Cambridge - flu

Citizen science experiment predicts massive toll of flu pandemic on the UK

sc604 — Thu, 22 Mar 2018 16:03:31 +0000

̽��ֱ��numbers are frightening, but even more daunting is the very real danger of a major flu pandemic emerging at any moment. Experts around the world agree that it’s a question of when not if the next deadly pandemic will strike, making it number one on the government civilian risk register in the UK.

When it happens the pandemic will almost certainly reach the UK and the government will be faced with a series of life-saving decisions. Should we close schools or public transport? Who should be given priority when the first doses of vaccine become available? How will we cope if there is a high mortality rate? Having the right answers to these and many other crucial pandemic response questions depends on mathematical models.

̽��ֱ��model behind the results, designed by researchers at the ̽��ֱ�� of Cambridge and the London School of Hygiene and Tropical Medicine, is based on data from nearly 30,000 volunteers and represents the largest and most comprehensive dataset of its kind. ̽��ֱ��results will be broadcast on Contagion! ̽��ֱ��BBC Four Pandemic, tonight (22 March) at 9pm on BBC Four, presented by Dr Hannah Fry and Dr Javid Abdelmoneim. ̽��ֱ��results are also published in the journal Epidemics.

“ ̽��ֱ��value of predictions hinges completely on the quality of the model,” said Professor Julia Gog from Cambridge’s Department of Applied Mathematics and Theoretical Physics, who heads the disease dynamics group. “Up to now, the picture of how the population in the UK move around has been surprisingly limited, and existing studies use relatively small samples of the population. Getting a handle on how people move and interact day to day is vital to understanding how a virus will actually spread from person to person and place to place. ̽��ֱ��BBC Pandemic project has aimed to address this gap, with volunteers using an app to track movements and record who they encounter day to day, creating the biggest dataset for UK pandemic research ever collected.”

“BBC Pandemic experiment has been hugely successful in recruiting study participants,” said Dr Petra Klepac, the lead author of the paper. “ ̽��ֱ��resulting dataset is incredibly rich and will become a new gold standard in modelling contact and movement patterns that shape the spread of infectious diseases. For the programme, we were able to create a detailed UK model based on data from almost 30,000 users.”

̽��ֱ��BBC Four programme will show how a pandemic might spread in the UK, starting from Haslemere in Surrey, where the team modelled in detail an introduction starting from a hypothetical patient zero.

“We don’t know of any studies that join up the movement and survey data so comprehensively,” said Gog. “And this experiment is just huge already, an order of magnitude bigger than anything even similar. ̽��ֱ��BBC Pandemic experiment sets a new benchmark for other future studies around the world.”

̽��ֱ��study remains open during all of 2018, and anyone in the UK can volunteer by using the app (available via App Store or Google Play). Once the project is complete, the anonymised dataset will be made available to all researchers, enabling more accurate prediction in future. “Our focus so far has been on a prospective influenza pandemic, but this dataset will be valuable in our efforts to understand and control a variety of infectious diseases, both in the UK and in extrapolating to other countries,” said Gog.

“While these preliminary results are eye-opening there’s a lot more this data can be used for,” said programme host Dr Hannah Fry. “Scientists around the country will be using it for years to come.”

̽��ֱ��BBC Pandemic app was launched in September 2017. Once downloaded, app users enter some basic anonymous demographic information about themselves such as age and gender, and then are asked to be tracked via the GPS on their phone once an hour for 24 hours. ̽��ֱ��app also records the people they come into close contact with. This is the first time tracking, demographic and contact data have been combined, making it an unrivalled tool for pandemic research.

̽��ֱ��headline results of the simulation shown in the programme are based on a moderately transmissible influenza pandemic virus with a high fatality rate, in accordance with a ‘reasonable worst case’. ̽��ֱ��details of assumptions and limitations are discussed in detail in the paper.

Reference
Petra Klepac, Stephen Kissler and Julia Gog. ‘Contagion! ̽��ֱ��BBC Four Pandemic – the model behind the documentary.’ Epidemics (2018). DOI: 10.1016/j.epidem.2018.03.003

How fast could a new flu epidemic spread? ̽��ֱ��results of the UK’s largest citizen science project of its kind ever attempted, carried out by thousands of volunteers, predict that 43 million people in the UK could be infected in an influenza pandemic, and with up to 886,000 of those infected expected to be fatalities.

We don’t know of any studies that join up the movement and survey data so comprehensively.

Julia Gog

Geographic patterns of spread of influenza pandemic

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Virus evolution and human behaviour shape global patterns of flu movement

cjb250 — Mon, 08 Jun 2015 15:00:18 +0000

In the study, an international team of researchers led by the ̽��ֱ�� of Cambridge and the Fred Hutchinson Cancer Research Center, and including all five World Health Organization (WHO) Influenza Collaborating Centres, reports surprising differences between the various types of seasonal flu virus, which they show to be due to the rate at which the different viruses evolve.

There are four types of influenza viruses that cause seasonal flu in humans: two influenza A viruses (H3N2 and H1N1) and two influenza B viruses (Yamagata and Victoria). While H3N2 viruses are the most common of the seasonal influenza viruses, H1N1 and B viruses also cause epidemics worldwide each year, hence the WHO selects representative strains of all four A and B viruses for inclusion in the seasonal influenza vaccine each year.

Importantly, all four of the viruses cause indistinguishable symptoms and evolve by similar mechanisms to escape immunity induced by prior infections and vaccinations. This ‘antigenic’ evolution is part of why people get influenza multiple times over the course of their lives.

In 2008, an international team led by scientists from the ̽��ֱ�� of Cambridge, writing in the journal Science, showed that H3N2 viruses circulate continuously in east and southeast Asia throughout the year, spreading to the rest of the world each year to cause seasonal flu epidemics. Given the fundamental similarities between H3N2, H1N1, and B infection it was thought that they would also emerge from east and southeast Asia to cause yearly epidemics worldwide. However, the work published today in Nature shows that in fact, H1N1 and B viruses behave very differently from H3N2 viruses.

Senior author Dr Colin Russell, from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge, UK, says: “While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide. This continuous circulation gives rise to a huge diversity in H1N1 and B viruses circulating globally.”

Interestingly, the researchers found that sometimes new H1N1 and B variants emerge from outside east and southeast Asia and are subsequently seeded into Asia, while in other cases H1N1 and B variants circulate in Asia for years without spreading globally.

“It’s really surprising to find that the H3N2 viruses are unique among the seasonal influenza viruses,” adds first author Dr Trevor Bedford from the Fred Hutchinson Cancer Research Center in Seattle, USA. “It’s almost as surprising to find that the differences among viruses are associated with a simple phenomenon: how quickly the viruses evolve antigenically.”

̽��ֱ��Nature study finds that the rate of global movement of each virus, and its ability to circulate continuously between epidemics, is shaped by how quickly that virus changes its coat to escape immunity in the human population. Viruses that evolve quickly, in particular H3N2, spread around the world rapidly, but die out quickly between epidemics. Viruses that evolve more slowly, like H1N1 and B viruses, spread around the world more slowly but are also better at circulating continuously between epidemics.

̽��ֱ��key element about global movement is who is getting infected: faster evolving viruses, like H3N2, can infect adults, who tend to travel more frequently than children, providing more opportunities for the virus to spread. Conversely, more slowly evolving viruses, such as H1N1 and B viruses, primarily infect children. Children get sick with all four seasonal flu viruses, but H3N2 evolves faster so it infects adults more often. This leads to a greater proportion of adult infections with H3N2 relative to H1N1 and B viruses, and faster spread of H3N2 viruses.

“Ultimately, this means that we can look at the viruses circulating in Asia to get a good idea of which H3N2 virus might spread worldwide, but for H1N1 and B it’s tremendously variable and the dominant variant can vary from one region of the world to another,” says Dr Russell.

̽��ֱ��Nature study also sheds important light on the role of India in the global spread of seasonal influenza viruses. Scientists and public health officials had long known that China and Southeast Asia were important for the evolution and spread of seasonal influenza viruses. However, based on the analysis of an extensive collection of viruses from India, it is now clear that India may be as central as China to the ongoing evolution of seasonal influenza viruses.

“ ̽��ֱ��focus of influenza research in the past has been on China and southeast Asia, but it seems obvious now that surveillance and public health in India, home to over one sixth of the world’s population, should be a high priority for further development to help safeguard India and the world against seasonal flu,” says Dr Mandeep Chadha of the National Institute of Virology, Pune, India.

̽��ֱ��research was primarily funded by the Royal Society and US National Institutes of Health with extensive involvement of the World Health Organization’s Global Influenza Surveillance and Response System.

Reference
Bedford, T et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature; 8 June 2015.

̽��ֱ��global movement patterns of all four seasonal influenza viruses are illustrated in research published today in the journal Nature, providing a detailed account of country-to-country virus spread over the last decade and revealing unexpected differences in circulation patterns between viruses.

While H3N2 viruses die out between epidemics and new viruses emerge from east and southeast Asia every year, H1N1 and B viruses frequently circulate continuously between epidemics worldwide

Colin Russell

Matteo Bagnoli

influenza

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Staying ahead of the game: Pre-empting flu evolution may make for better vaccines

cjb250 — Thu, 20 Nov 2014 19:00:02 +0000

In a study published today in the journal Science, the researchers in the UK, Vietnam, ̽��ֱ��Netherlands and Australia, led by the ̽��ֱ�� of Cambridge, describe how an immunological phenomenon they refer to as a ‘back boost’ suggests that it may be better to pre-emptively vaccinate against likely future strains than to use a strain already circulating in the human population.

Influenza is a notoriously difficult virus against which to vaccinate. There are many different strains circulating – both in human and animal populations – and these strains themselves evolve rapidly. Yet manufacturers, who need to produce around 350 million doses ahead of the annual ‘flu season’, must know which strain to put in the vaccine months in advance – during which time the circulating viruses can evolve again.

Scientists at the World Health Organisation (WHO) meet each February to select which strain to use in vaccine development. Due to the complexity of human immune responses, this is decided largely through analysis of immune responses in ferrets to infer which strain best matches those currently circulating. However, vaccination campaigns for the following winter flu season usually start in October, by which time the virus may have evolved such that the effectiveness of the vaccine match is reduced.

“It’s a real challenge: the WHO selects a strain of flu using the best information available but is faced with the possibility that the virus will evolve before the flu season,” explains Dr Judy Fonville, one of the primary authors on the paper and a member of WHO Collaborating Centre for Modelling, Evolution and Control of Emerging Infectious Diseases at the ̽��ֱ�� of Cambridge. “Even if it does, though, it’s worth remembering that the flu vaccine still offers much greater protection than having no jab. We’re looking for ways to make an important vaccine even more effective.”

According to the WHO, seasonal influenza causes between 3 and 5 million cases of severe illness each year worldwide, up to 500,000 deaths, as well as significant economic impact. Vaccination policies vary per country, but are typically recommended for those at risk of serious complications, such as pregnant women and the elderly. ̽��ֱ��seasonal flu vaccine has been described as one of the most cost-effective measures of disease prevention, and vaccination therefore has a large health economic benefit. Currently 350 million people partake in annual vaccination programmes. Yet there is room for improvement.

After gathering an extensive amount of immunological data, the team modelled the antibody response to vaccination and infection using a newly developed computer-based method to create an individual’s ‘antibody landscape’. This landscape visualises an individual’s distinct immune profile like a three dimensional landscape with mountains in areas of immune memory and valleys in unprotected areas. ̽��ֱ��technique enables a much greater understanding of how our immune system responds to pathogens such as flu that evolve and re-infect us.

A key finding from the work is that upon infection, a response is seen not just to the infecting influenza strain, but to all the strains that an individual has encountered in the past. It is this broad recall of immunity, that they term the ‘back-boost’, that is the basis for the proposed vaccine improvement.

Dr Sam Wilks, one of the primary authors, explains: “Crucially, when the vaccine strain is updated pre-emptively, we see that it still stimulates better protection against future viruses yet this comes at no cost to the protection generated against currently circulating ones.

“Faced with uncertainty about how and when the flu virus might evolve, it’s better to gamble than to be conservative: if you update early, you still stimulate protection against current strains – much worse is if you update too late. Rather than trying to play ‘catch-up’, it’s better to anticipate and prepare for the likely next step of influenza evolution – and there is no penalty for doing it too soon.”

Professor Derek Smith, also from Cambridge, adds why this may lead to improved vaccines in a relatively short timeframe: “ ̽��ֱ��beauty of this approach is that it would not require any change to the current manufacturing process. From the point that the new strain has been selected through to an individual receiving their shot, the steps will be exactly the same. ̽��ֱ��only difference would be greater protection for the recipient.”

̽��ֱ��team is now combining this research with their other work on predicting the way in which the virus will evolve, and plan to combine these two major pieces of work in prospective clinical trials.

̽��ֱ��international collaboration included researchers from: the Erasmus Medical Center, the Netherlands; the Oxford ̽��ֱ�� Clinical Research Unit & Wellcome Trust Major Overseas Programme and the National Institute of Hygiene and Epidemiology, Vietnam; and the WHO Collaborating Centre for Reference and Research on Influenza at the Victorian Infectious Diseases Reference Laboratory in Melbourne. Its principal funders were the Wellcome Trust and the US National Institutes of Health Centers of Excellence for Influenza Research and Surveillance (CEIRS).

Reference
Fonville, JM et al. Antibody landscapes after influenza virus infection or vaccination. Science; 20 Nov 2014

An international team of researchers has shown that it may be possible to improve the effectiveness of the seasonal flu vaccine by ‘pre-empting’ the evolution of the influenza virus.

Faced with uncertainty about how and when the flu virus might evolve, it’s better to gamble than to be conservative

Sam Wilks

Daniel Paquet

Flu Vaccination Grippe (cropped)

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Scientists ‘must not become complacent’ when assessing pandemic threat from flu viruses

cjb250 — Wed, 15 Oct 2014 12:30:00 +0000

Influenza pandemics arise when a new virus strain – against which humans have yet to develop widespread immunity – spreads in the human population. There have been five such pandemics in the past 100 years, the worst of which – the 1918 Spanish Flu – cost 50 million lives worldwide. Of these pandemics, three are thought to have spread from birds and one from pigs. However, pandemic influenza strains represent only a tiny fraction of the total diversity of influenza viruses that exist in nature; the threats posed by the majority of these viruses are poorly understood. Assessing which viruses pose the greatest risk of causing the next human pandemic is an enormous challenge.

Steven Riley from Imperial College London, an author of the study, says: “There are too many strains of influenza viruses out there in non-human hosts to make it feasible to make preparations against each one. Instead, we need to get better at assessing the pandemic risks so that we know where best to focus our efforts. At the moment, this assessment is largely driven by a simple idea: animal viruses that cause sporadic human infections pose a greater risk than viruses that have not been documented to infect humans. But in fact, none of the viruses that caused the major pandemics of the last century were detected in humans before they emerged in their pandemic form.”

Writing in the journal eLife, the scientists set out the steps that they consider necessary to increase our ability to assess pandemic risk. As influenza virus genome sequencing becomes cheaper, faster and more readily available, the data it generates has the potential to transform the research community’s ability to predict the pandemic risk. However, it remains extremely difficult to predict just from a virus’s genome what symptoms it will elicit in its host – and hence how deadly the virus is. ̽��ֱ��researchers call for better integration of experimental data, computational methods and mathematical models, in conjunction with refinements to surveillance methodology.

However, they say that scientific insights into non‐human influenza viruses must not give way to complacency that the most substantial threats have been identified and characterized. They point out that several recent strains including the 2009 H1N1 “swine flu” pandemic virus and the recently emerged H7N9 viruses in China highlight the importance of remaining vigilant against as-yet unrecognized high risk viruses and the value of surveillance for influenza viruses in humans.

“No one can say with anything close to a hundred percent certainty when or where the next pandemic will start or which virus will cause it,” says Dr Colin Russell from the Department of Veterinary Medicine at the ̽��ֱ�� of Cambridge. “We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner.

“We need to be prepared for a swift response, with coordinated action, to help mitigate the spread of the next pandemic virus. Without developing this ability to respond, we will have spent billions building systems just for watching the next pandemic unfold.”

̽��ֱ��research was supported in part by the Research and Policy for Infectious Disease Dynamics program of the US Department of Homeland Security and the National Institutes of Health.

Reference
Russell, CA et al. Improving pandemic influenza risk assessment. eLife; 15 Oct 2015

As our ability to assess the pandemic risk from strains of influenza virus increases with the latest scientific developments, we must not allow ourselves to become complacent that the most substantial threats have been identified, argue an international consortium of scientists.

We are getting much better at identifying and assessing potential threats, but we must be vigilant about surprises lurking around the corner

Colin Russell

MIKI Yoshihito

New influenza viruses (cropped)

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Researchers to explore the role of wild birds in the spread of avian flu viruses

gm349 — Thu, 06 Jun 2013 09:55:04 +0000

A new initiative to study the spread of avian flu by wild bird populations launched today at Ilia State ̽��ֱ�� in Georgia. ̽��ֱ��three-year international collaboration will examine the ecology and evolution of avian influenza viruses in their natural hosts, waterfowl.

Aquatic birds are the natural reservoir for influenza A viruses. However, these viruses can sometimes infect other animals such as pigs and humans, potentially resulting in an epidemic or even a pandemic because the new host species doesn’t have immunity to these avian flu viruses.

This ever-present risk means it is important to understand what flu viruses circulate in wild birds, and what risk these viruses might pose to other animal species. In addition, occasionally when avian flu viruses infect poultry they can mutate into a more deadly form of flu. This highly pathogenic strain of avian flu is not only more deadly in birds than other avian flu viruses but is also more deadly than the common seasonal human flu if it infects people.

Since the emergence and westward spread of the highly pathogenic A/H5N1, one of the unanswered questions is what role wild birds, particularly long-distance migrants, play in the dissemination of influenza A viruses from Southeast Asia to other geographic regions. As Georgia bridges Western Asia and Eastern Europe and is home to wild water birds from many different parts of Eurasia during migration and winter, it is an ideal location to undertake the research.

To find out more about how the viruses spread, the researchers will map circulating avian flu strains in birds in the region as well as studying the movements and population structure of the birds themselves as currently, very little is known about the migratory routes wild birds take to reach breeding and overwintering grounds.

Dr Nicola Lewis, lead researcher on the project from the ̽��ֱ�� of Cambridge, said: “Three migratory flyways converge in the Caucasus region so avian flu viruses that had been infecting birds in one part of Asia might get the opportunity to spread to birds flying in from other regions, and we think that this is most likely to happen in places such as Georgia, where birds from many different parts of Eurasia mix in large numbers during migration and during the winter.

“Knowing where bird populations fly will ultimately allow us to assess what risk might be for an avian flu virus, particularly a deadly one, in one region being taken by a wild bird as it migrates to another region in Asia.”

̽��ֱ��Cambridge researchers will be working with leading Georgian scientists to address these key questions about avian flu viruses in wild water birds.

Lewis added: “By understanding how these avian flu viruses evolve in wild birds and the risk wild birds might pose in spreading infectious diseases, this international scientific collaboration will inform both global animal and public health.”

As well as improving avian influenza virus surveillance in the region, the project will also increase the diagnostic and scientific expertise in Georgia by training local Masters students, academics and laboratory staff to use state-of-the art infectious disease analyses. Integrating Georgia more fully into the international scientific influenza community will provide a much more comprehensive picture of the spread of avian flu.

̽��ֱ��collaboration includes the ̽��ֱ�� of Cambridge, the Animal Health and Veterinary Laboratories (AHVLA) in the UK, Ilia State ̽��ֱ��, the Georgian National Centre for Disease Control and Public Health, the Laboratory of the Ministry of Agriculture of Georgia and the Richard G. Lugar Center for Research in Tbilisi, Georgia.

Scientists focusing on the ecology and evolution of avian flu.

Knowing where bird populations fly will ultimately allow us to assess what risk might be for an avian flu virus, particularly a deadly one, in one region being taken by a wild bird as it migrates to another region in Asia.

Dr Nicola Lewis, lead researcher on the project from the ̽��ֱ�� of Cambridge

Waterfowl

USFWS Pacific Southwest Region from Flickr

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