From pandemic to policy: combating swine flu

Pandemic H1N1 virus infection – or ‘swine flu’ – has spread globally following its emergence in Mexico in March 2009. Millions of people have been infected and, as of December 2009, over 12,220 deaths have been reported to the World Health Organization (WHO).

Governments and individuals are understandably concerned: this is the first human influenza pandemic in more than 40 years. Although a ‘bird flu’ pandemic has been feared since 1997, no more than a few hundred people died of avian H5N1 influenza, despite being spread by migratory birds and the international poultry trade. Putting this in context, hundreds of thousands of people globally continue to die from seasonal influenza each year.

Not only do severe pandemics have far-reaching repercussions for human health, the health sector and the economy, but influenza outbreaks in farmed animals also have a profound impact on the consumer market and loss of business. New research on the origins, spread and prevention of swine flu is urgently needed to inform government policy on how future pandemics like the one we are currently experiencing can be detected, controlled and ultimately prevented.

A coordinated research response

In what has been described as among the fastest reactions of the UK science and funding community to an emerging disease threat, leading UK research funders announced in November 2009 funding of £7.5 million aimed at understanding the development and spread of pandemic influenza. This coordinated response from the research community was catalysed by the Medical Research Council (MRC), Wellcome Trust, Biotechnology and Biological Sciences Research Council (BBSRC), Department of Health and Department for Environment, Food and Rural Affairs (Defra). The result has been the funding of four major collaborative projects (see below).

In Cambridge, Professor James Wood at the Department of Veterinary Medicine leads a study to monitor the spread and evolution of influenza in infected UK pig herds and farm workers, bringing together a multidisciplinary team of 18 researchers from Cambridge, Oxford, Edinburgh and London. A sister project led by Professor Ian Brown at the Veterinary Laboratories Agency (VLA), Weybridge, focuses on the transmission, infection dynamics and immunopathology of H1N1 in pigs compared with human infection. Together, the two projects form the Combating Swine Influenza (COSI) Initiative.

Viral ‘mixing vessels’

The new research builds on a programme of study carried out by the Cambridge Infectious Diseases Consortium (CIDC), which has been investigating infectious animal viruses that pose a major disease threat to both animal and human populations. The CIDC is led by Professor Wood in the Department of Veterinary Medicine and operates in close collaboration with the Animal Health Trust (AHT) in Newmarket.

A large part of research within the CIDC focuses on swine H1N1 and equine H3N8 viruses. Swine flu is common in pigs in Europe and circulates through farms on at least an annual basis. Equine influenza virus also circulates endemically in the UK, predominantly affecting younger horses. Working closely with the international and national reference laboratories for swine and equine influenza – the VLA and the AHT, respectively – and collaborating with the Wellcome Trust Sanger Institute, researchers at the CIDC are aiming to examine genetic variation within endemic viruses.

This latest strain of swine flu, for instance, is known to have arisen from the combination of two swine influenza viruses, one originating in the USA and the other in Europe. It seems that progenitor viruses were circulating undetected, probably in pigs, for around nine years before the jump to humans took place. Pigs are especially likely to be a ‘mixing vessel’ for viruses because they are more susceptible to a range of influenza viruses than most other animals.

By examining genetic variation within endemic swine and equine viruses, the scientists hope to understand how virus variants, which usually arise at a low frequency, end up being spread between animals and populations. Using epidemiological and experimental data, they are constructing mathematical models of virus infections, examining questions relating to the control of infection within the host animal, the spread and control of viruses through populations and how the gradual evolution of the influenza virus reaches a threshold before large-scale outbreaks or epidemics are likely to be observed.

The COSI Initiative

The newly funded research initiative is intended to develop a vital new understanding of how the pandemic H1N1 virus behaves in pig populations and how interaction with farm workers may help it to evolve and spread. With this information, it should be possible to move a step closer to developing strategies to slow or prevent the spread of the virus in both pig herds and the human population.

The collaboration led by Professor Wood aims to define the consequences of what would happen if the pandemic H1N1 virus spreads from humans to pigs, as has happened in countries as diverse as Argentina, USA, Canada, Northern Ireland and Australia, probably following the infection of pig farmers who have then transmitted the virus to pigs. In Britain, many pigs are farmed in large populations and, if these farms were to become infected with the pandemic flu virus, then large amounts of virus would be produced with unpredictable consequences.

Detailed genetic studies of archived samples from previous swine influenza outbreaks will be carried out, as well as an investigation of the health of pig farmers and vets who are exposed through their occupation to these outbreaks. This will provide a better explanation of how the pandemic virus arose and spread, including where the initial virus combination took place. With this information, the likelihood of similar events reoccurring can be predicted and recommendations for minimising the ongoing risk can be made.

Another important area will be to predict the immediate threat if the pandemic virus mutates to become a more virulent form, particularly if pandemic H1N1 becomes endemic in the pig population. The rates of viral mutation will be studied and any specific virus mutations associated with the spread between pigs and people working with pigs will be identified. Data from affected farms will be used to make accurate models of transmission and dynamics to help inform intervention strategies.

Informing policy

Together, the four newly funded collaborative projects aim to understand how the virus mutates and jumps the species barrier and how it spreads through communities; how the virus causes disease in both pigs and humans and why it affects some individuals more than others; and which interventions are most effective at preventing infection or treating the disease. The intention is for the results to feed directly into wider policy analysis on dealing with pandemics, for the long-term benefit of human and animal health.

‘This is amongst the fastest I have ever seen the UK science community react to an emerging disease threat. Turning around a funding initiative in a matter of months while ensuring we are supporting the best science has been a huge achievement by the scientific community and the funders.’ Professor Douglas Kell, BBSRC Chief Executive, commenting on four new collaborative projects being funded across the UK, one of which is being led by Cambridge.