It's another cheerful week in Nature's editorial pages. In its May 26, 2005, issue, the magazine devoted that space to a special section on avian influenza, under the title: Are We Ready?

The near unanimous answer from several experts is no.

H5N1 is the highly lethal strain of avian influenza that is thought to be the lead candidate for initiating another flu pandemic, which experts agree is long overdue. So far, most of the reported deaths from H5N1 stem from bird-to-human transmission. But if H5N1 acquires the ability to spread easily from human to human, it could be deadly.

Albert Osterhaus and his colleagues at the Erasmus Medical Centre in Rotterdam, the Netherlands, write that in a new pandemic, there could be 30 million sick and 7 million dead - and that's the optimistic prediction. In more pessimistic scenarios, the pandemic could sicken 20 percent of the global population, and its death toll could easily rival that of the 1918-1919 "Spanish" Flu pandemic that killed 40 million people.

The U.S. is unprepared for such a pandemic. Vaccines for H5N1 are all in early stage clinical trials, if that, and U.S. stockpiles of F. Hoffmann-La Roche Ltd.'s Tamiflu (oseltamivir), which is effective against H5N1, are enough to treat just 1 percent of the population, or one-fiftieth the recommendation of the Infectious Disease Society of America. (See "House Members Hear Testimony On Pandemic Flu Preparedness," this issue.)

The opinion that there will be a pandemic at all might seem fatalistic, but it is probably correct, sooner or later. Still, as Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, pointed out in his editorial, "We cannot predict exactly when a pandemic will occur, nor can we know for certain whether the culprit will be H5N1 or a related virus."

In another editorial, Robert Webster and Diane Hulse, researchers at the St. Jude's Children's Research Hospital in Memphis, Tenn., suggested that there are strategies to reduce the chance that a pandemic will be caused by the highly lethal H5N1.

They wrote that "a global strategy for preventing pandemics at their source - in the animals, mostly poultry, that carry the virus - has received relatively little attention." They said that the "aim must be to reduce the virus load in ducks below the transmissible level," and added that it "is probably the approach that has the best chance of reducing the inevitability of H5N1 acquiring consistent human-to-human transmission."

Even if such consistent human-to-human transmission is not prevented, delaying it might buy time that could be used to better prepare. Hulse and Webster said many experts believe a pandemic already would have occurred if Hong Kong had not culled - a polite word for killed - its entire poultry population of more than 1 million birds within three days when the first instance of bird-to-human infection with H5N1 was documented there in 1997.

They also wrote that while H5N1 is endemic to poultry in both Vietnam and Thailand, along with other South Asian nations, "since December 2004, 41 people have been infected with H5N1 in Vietnam and 16 have died, but none have been infected in Thailand." The reason: massive culling of ducks in Thailand. "Thus," they concluded, "reducing H5N1 infection in poultry clearly reduces the threat to humans." They concede that vaccinating birds does influence the evolution of the virus but not that such evolution is happening under any circumstances.

Culling Vs. Vaccination

To date, culling has remained the most effective way of reducing the risk of avian flu. That's because the quality of vaccines varies strongly. Hulse and Webster wrote that "the few comparative tests that have been done on agricultural vaccines from different suppliers show that some are good and some are bad. Bad vaccines prevent the symptoms of disease but not virus excretion, which can lead to later infection."

However, good vaccines that can prevent virus excretion do exist and have been used successfully in Hong Kong and China, among other places. Earlier this year, animal health care company Merial Ltd., of Duluth, Ga., a joint venture between Merck & Co. Inc., of Whitehouse Station, N.J., and Paris-based Sanofi-Aventis Group, introduced a new inactivated chicken vaccine that protects against H5N1. One of its advantages is that vaccinated birds can be distinguished from infected animals via a serological test.

Culling also has its own drawbacks. For one thing, given that H5N1 does not respect national borders, even if a country manages to control the virus within its borders by culling one season, the virus is likely to make a comeback from neighboring countries the next year.

Another challenge is economic rather than scientific: the Food and Agriculture Organization of the United Nations reports that "culling birds in order to eradicate and control the spread of [H5N1] is having a negative impact on the livelihoods of all classes of poultry owners and producers and their employees. Such an impact is most serious on the smaller, family-operated commercial producers for whom poultry production is their sole source of income generation. That fact has been specifically reported from Vietnam." In other words, a rational risk-benefit-analysis of culling one's livestock and losing one's sole source of income, vs. a currently still-small possibility of being infected with H5N1, will lead to different conclusions by the Vietnamese farmer and the Dutch epidemiologist.

In their Nature piece, Hulse and Webster concluded that though poultry vaccines, particularly for ducks, need to be improved to be a realistic match for culling, "it may be that high-quality vaccine strains matched to the circulating strains can reduce the level of circulating virus below the transmissible level. The technology for producing inexpensive agricultural vaccines using reverse genetics is available and should be developed."

Hopefully, such developments will come in time to make a difference.