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'More research needed on every possible front' is the conclusion of leading bird flu researchers writing today (21 April) in a special section in Science.

They discuss progress and shortfalls in four major research fields relating to the disease.  

Ron Fouchier and colleagues review what is known about the virus in wild birds, and their role in spreading the disease.

Roland Regoes and Sebastian Bonhoeffer look at how avian flu viruses become resistant to drugs.

Derek Smith discusses the importance of fine-tuning mathematical models being used to predict the spread of a pandemic.

Finally, Thijs Kuiken and colleagues look at what is known about the factors stopping bird flu viruses from infecting people.

Migratory birds contribute to the spread of the virus across the globe, and infections in wild birds are often the first sign of its arrival in new regions.

But Fouchier and colleagues say the little we know about the virus in wild birds gives "no scientific basis" for culling wild birds to control outbreaks.

Regoes and Bonhoeffer point out that researchers know little about how drug-resistant viruses are transmitted between humans.

As a result, it is hard to predict whether giving large groups of people antiviral drugs during a pandemic outbreak — as planned by the World Health Organization — would cause drug-resistant viruses to emerge.

They say experimental, epidemiological and computer model studies are needed to address the question.

Smith says computer models are invaluable as they help policymakers decide how much of a drug or vaccine needs to be stockpiled, how to distribute them, and what quarantine measures to take.

But he worries that scientists do not test their pandemic models. He says more data should be collected from outbreaks of seasonal flu and used to test models that predict the spread of pandemics.

Kuiken and colleagues highlight the need to understand how and why some pathogens become capable of infecting new species.

The H5N1 virus's potential for affecting human health depends entirely on whether it can change to become capable of infecting people, replicating inside them, and being transmitted between them.

Scientists understand some of the factors that could allow this to happen — for instance, they know that certain changes in the virus's genetic material can help it to infect human cells.

But many other issues remain unclear. These include which genetic changes are needed to help bird flu spread efficiently between people, which factors would make it capable of causing a pandemic, how versions of the virus carried by one person differ, and what the implications of this are.

Answering these questions will not only help tackle influenza viruses in future, but also increase our understanding of how viruses in general jump from one species to another.

Link to full paper by Fouchier's team in Science

Reference: Science 312, 384 (2006)

Link to full paper by Regoes and Bonhoeffer in Science

Reference: Science 312, 389 (2006)

Link to full paper by Smith in Science

Reference: Science 312, 392 (2006)

Link to full paper by Kuiken et al. in Science

Reference: Science 312, 394 (2006)

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