25 October 2002 18:42 GMT

by Julie Clayton

[caption and credit]

Malta - There's no doubt in the minds of researchers who attended this week's First European Influenza Conference here: the emergence of a new strain of flu virus that could sweep across the globe killing millions is going to happen - sometime.

The conference marked the 10th anniversary of the European Scientific Working Group on Influenza (ESWI), which has seen its role change dramatically from focusing on basic research to making demands for European-level preparedness for the next pandemic.

Flu experts across Europe have been working overtime to give decision-makers in Europe and the rest of world a wake-up call to "always expect the unexpected" when it comes to the influenza virus. The infection's impact, they warn, is likely to be far greater than any bioterrorist attack.

Unable to predict when the next pandemic will occur, researchers believe they can draw many useful lessons from past outbreaks, particularly by studying the genes carried by the 1918 "Spanish flu" pandemic strain, which killed 50 million people worldwide, and the 1997 Hong Kong outbreak which killed six. At least one of these - the NS1 gene, may have some effects in common with other highly virulent pathogens, including the Ebola and Lassa fever viruses.

Surveillance experts attending the meeting wasted no time dispelling some of the great flu myths. First of all, on a global scale, it does not only happen in wintertime - flu is a year-round phenomenon. There are major peaks of incidence in the winter months in the Northern and Southern hemispheres, but it is at relatively constant levels year-round in the tropics. And, as John Oxford, professor of virology at Queen Mary College, London, notes, the great 1918 pandemic first emerged in Europe in the summer month of June.

Year-round surveillance is therefore the only way to gain any advanced warning to individual nations about the nature of circulating viruses. In particular, information about the disease, and the viruses causing it, needs to be brought together, for the most effective vaccine recommendations to be made.

Another myth is that experts should only look to South East Asia - China and Hong Kong - as the source of the next pandemic. Indeed, an outbreak could occur anywhere, including Africa and the Middle East.

But China and Hong Kong continue to provide invaluable lessons. Here, many people are in contact with live birds, particularly chickens and ducks, at poultry farms and live bird markets. The 1997 Hong Kong outbreak shocked flu experts by demonstrating, for the first time, that flu viruses could jump the species barrier directly from birds to humans. Until this happened, attention had focused on pigs as the "mixing vessel" for avian and mammalian viruses to re-assort before infecting human hosts.

But as Albert Osterhaus, president of the European Scientific Working Group on Influenza highlighted, the natural reservoirs are more likely to be migratory birds and waterfowl rather than domesticated animals. These include gulls, ducks, and geese, which carry the viruses, often without ill effect, in their gastrointestinal tracts. Their droppings can fall not only on land, but also into seas, rivers, and lakes, to form what Osterhaus calls a "poop soup" capable of infecting aquatic mammals, too - including seals.

Yet another myth is that protection against flu depends entirely on antibodies. Cell-mediated immunity, including CD8 killer T cells, and the first line defenses of the innate immune system, are also likely to play an important, though relatively unexplored role. New live vaccines now in the pipeline are intended to trigger this type of response.

Meanwhile, conventional flu vaccines contain inactivated viruses that trigger antibodies. But unless manufacturers switch to more rapid production methods or find ways to make existing preparations stretch further, delegates heard, vaccines will not be available soon enough, or in sufficient quantity, to cope.

The arrival of new antiviral drugs on the market, however, promises an effective treatment for infected individuals, agreed scientists and clinicians attending the meeting. These are suitable for the regular flu epidemics that strike all the time, but they also provide the first opportunity for nations to build up efficacy in advance of the next big one.

By contrast with the victims of last century's 1918, 1957, and 1968 pandemics, those affected by the next one, "will not go quietly," concluded Oxford.

Picture caption:
In background: Photomicrograph of Hemophilus influenzae, CDC.

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