By Ray Dunne
BBC News Online health staff
It is only a matter of time before a major outbreak of potentially deadly flu, according to scientists. Could the world cope?
A new virus could spread quickly
There have been three flu pandemics during the past 100 years.
The 1918 Spanish flu is estimated to have killed up to 50m people worldwide.
The Asian flu of 1957 was caught much earlier but still claimed one million lives. The Hong Kong flu of 1968 was responsible for a similar number of deaths.
It has been 37 years since the last major outbreak and scientists, health professionals and some governments are getting twitchy.
Most scientists agree that another flu pandemic is inevitable. Many say it is overdue.
"It really is inevitable," says Dr Alan Hay, director of the World Influenza Centre in London. "We don't know when it will arrive but we are anticipating it."
Some experts believe the next killer flu may already have arrived.
"Avian flu might yet be the next pandemic virus," says John Oxford, professor of virology at St Bartholomew's and the Royal London School of Medicine.
The latest outbreak of bird flu in Asia has killed about 50 people. Millions of chickens have been slaughtered.
Bird flu is seen as a potential threat
There has been no confirmed case yet of this particular strain of the virus being passed from human to human.
However, scientists are worried that the virus could mutate and could pass from one person to another, triggering a possible pandemic.
Those fears are not groundless. Dutch scientists say three people who caught bird flu when a different strain hit the Netherlands in 2003 may have caught it from people and not animals.
The World Health Organization has been urging the international community for years to prepare for the next flu pandemic.
It estimates a future outbreak could kill as many as 650,000 people in industrialised countries. The figure would be significantly higher in the developing world.
Recent outbreaks of bird flu and Sars have spurred some countries into action. However, others are lagging behind.
"The WHO has been desperately trying to get countries to take this seriously," Professor Oxford says. "It has 192 members but only 12 have done anything about it.
"People really need to think about what happens when this virus arrives - who is going to do what; what vaccines are available; who is going to distribute them and who is going to bury people when they die."
In early 2004, Canada, which was hit hard by Sars, outlined its plans for dealing with a flu pandemic. The 450-page document spells out what actions authorities will take in the event of an outbreak.
Four years ago, ministers signed a deal with a local pharmaceutical company to provide a vaccine for 32m Canadians in the event of a pandemic.
Other countries have taken similar steps. In Germany, the government has drawn up plans to dispense millions of doses of the antiviral drug Tamiflu.
1918 Spanish flu killed 50m
1957 Asian flu killed around 1m
1968 Hong Kong flu killed 1m
2003 Sars killed 774
2004-5 Avian flu (H5N1) has killed 50 to date
The UK government is taking similar action. "We are taking active steps to increase our stocks of available antivirals," says a spokesman for the Department of Health.
In a report in 2003, the WHO said countries needed to do more.
"A few member states are formulating national plans for pandemic preparedness, but only one country has completed a formal, legally sanctioned plan.
"The absence of such national plans, including projected needs for vaccines, antiviral drugs, and other essential supplies, hinders efforts to coordinate preparedness planning at the global level."
It added: "All countries need to be aware of the need to begin preparedness planning well in advance of a pandemic, as many essential activities take considerable time."
The WHO will spearhead the international response to any flu pandemic.
Some 110 national influenza reference centres in 83 countries are acting as its eyes and ears, feeding into four collaborating centres in Atlanta, London, Melbourne and Tokyo.
"There is very intense surveillance to detect any novel viruses," says Dr Alan Hay.
One of the biggest challenges facing scientists if and when a powerful strain of flu emerges will be to find a vaccine to protect people against it.
Scientists around the world are already working on possible vaccines for Sars and avian flu - two of the leading contenders for the title of next pandemic virus.
"We have a sort of hierarchy of likelihood viruses that may spark a pandemic," says Dr Hay.
Experts say a pandemic may be imminent
"We have some vaccine prepared against some of these viruses. We hope they will give us a head start."
The vaccines are in very early stages of development and are based on strains of influenza that have emerged in recent years but have not sparked major outbreaks.
The hope is they can provide the basis of an effective vaccine in the event of a pandemic.
Like all new drugs, any vaccine for flu - even one for a particularly lethal strain of the virus - will take time to develop and to be made available to the public.
"It is difficult to say how long it could take," says Dr Hay.
Some experts believe a vaccine could become available relatively quickly. Others maintain it will take a year or more after the virus hits.
However, experts are hopeful that some existing drugs could provide an important first line of defence against a future pandemic.
A study published in early 2004 by scientists in Australia suggests Relenza is effective against the strain of bird flu currently affecting Asia.
The GlaxoSmithKline drug has been available since 1999 and stops the flu virus from spreading. Tamiflu, which is manufactured by Hoffmann-La Roche, works in a similar way.
Professor Oxford believes governments around the world should be stockpiling these drugs now.
"These drugs act against every known influenza virus. There is no excuse for governments not to have them," he says.
"There will be a mad rush for these drugs if this flu arrives on the scene. It will be pretty chaotic.
"It will be a dereliction of duty not to have stockpiled these drugs."