An influenza pandemic, when it arrives, will be an immediate threat to the health of nearly everyone on Earth, but very little is being done to prevent its potential devastation, say experts who met this week at the World Health Organization's headquarters in Switzerland.
A vaccine is unlikely to prevent the global spread of a pandemic strain of flu virus, but it could save millions of lives. To do so, the world must be ready to make, test, pay for, distribute and probably share what will be a scarce supply, the experts concluded.
"We have a unique window of opportunity now to get our homework done to ensure that, when it matters most, vaccine production can happen immediately," said Klaus Stohr, the leader of WHO's influenza activities, who chaired the two-day, closed-door meeting that ended yesterday. "That's our chance, and we don't want to miss that chance."
In a telephone news conference, Arlene King, an official in Canada's public health agency, said a pandemic, or global epidemic, will be "a national health/security issue. It will be the largest public health infectious-disease emergency we ever face in most countries, and certainly globally."
Avian influenza -- "bird flu" -- is the latest strain of concern. The A/H5N1 virus, which has spread widely among chickens and ducks, has infected 44 people in Thailand and Vietnam this year, killing 32. Should it adapt fully to humans and be capable of easy person-to-person transmission, it would probably spread worldwide in three to six months.
"We have in Asia an H5N1 virus which is ready to cause a pandemic," Stohr said.
If the three flu pandemics in the 20th century are models, one-fifth to one-third of the world population might be infected in the next one. Even if only 1 percent were to die, as some experts predict, it would cause huge social and economic disruption. The "Spanish flu" pandemic of 1918-1919 killed at least 50 million people.
The meeting, attended by about 50 people from national health ministries, drug regulatory agencies, and vaccine companies, was held to lay out the obstacles to developing a pandemic vaccine and begin the work of overcoming them.
WHO has no authority to compel countries or companies to act. There was consensus that not nearly enough money is being spent on planning for a pandemic -- and that governments must take the lead.
"Market forces have not brought companies into pandemic vaccine development. That's something that has been clearly recognized," Stohr said.
At the moment, only the United States has ordered up production of vaccine against bird flu -- a move that even on a small scale constitutes an expensive gamble. The Department of Health and Human Services has contracted with two companies to make about 2 million doses of vaccine against the currently circulating H5N1 strain, but they might not be usable when a pandemic hits. Tests of its safety and effectiveness in people will be conducted by April.
The obstacles to making an adequate supply of vaccine are immense. They span the spheres of science, technology, law, politics and ethics.
Scientists will need both widespread surveillance and rapid genetic analysis of new strains if they have a chance of catching a pandemic early enough to produce a useful vaccine. Scientists also need to know whether much smaller doses than usual might still be protective, which would stretch a limited supply of vaccine.
Vaccine companies will need to make "speculative" pandemic vaccines in small quantities while not jeopardizing their annual production of conventional flu shots, the experts said. They will also need access to techniques -- some covered by patents -- that will let them rapidly create vaccine seed through a process called "reverse genetics."
Government vaccine-licensing agencies, such as the Food and Drug Administration, will need the ability to rapidly evaluate flu vaccines made elsewhere -- or agree to let them in automatically once they are approved elsewhere. Countries also must decide whether they are willing to share vaccine, and in particular send their supply to the front line of a foreign outbreak in hopes of slowing the virus's spread.
At home, governments will need to decide who will get flu shots when there are too few to go around -- and when the stakes are much higher than they are this season, when the United States is facing a similar problem.
Asked who would need to be vaccinated, Stohr answered: "Practically everybody."
A pandemic vaccine would need to protect against only one strain of flu virus -- the newly emerged one -- rather than three strains, as is the case with the annual flu shot. However, because nobody on Earth would have underlying immunity to the new strain, people would need to get two shots to be protected.
Only about a dozen companies in the world make flu vaccine. Aventis Pasteur, which has its headquarters in France, makes about half the world's production, which last year totaled 292 million doses. It will probably be less this year, as the second-largest producer, the American biotech company Chiron, lost its license to sell 48 million doses because of manufacturing problems at its plant outside Liverpool, England.
The industry's ability to make vaccine against a pandemic strain is linked to its ability to make conventional flu vaccine. Plants that make other vaccines -- such as for measles or hepatitis -- cannot be converted to make one for influenza. For that reason, many experts believe it is important that more people take yearly flu shots -- and thereby encourage companies to add production capacity.
Making seed strains and test batches of vaccine for emerging flu viruses, however, is financially risky because the pandemic strain that emerges may be substantially different from any in development.
For example, the bird flu strain being used in the experimental U.S. vaccine is different enough from H5N1 strains that killed people in Hong Kong in 1997 and 2003 that virus seed from those earlier outbreaks could not be used. It took months to make a new one that reflected the continuing evolution of the virus.
Such ongoing preparation is "an investment without any return, which costs millions of dollars or euros, which compete with other priorities in the industry," said Luc Hessel, an Aventis Pasteur executive who attended the Geneva meeting and spoke to reporters after it.