Pandemic influenza response: Dilemmas of preparedness and equity loom large

April 2006

ATLANTA — The avian influenza strain H5N1 has been spreading quickly in birds, and appears more pathogenic than when it first emerged in 1996, according to Keiji Fukuda, MD, who spoke here at the 2006 International Conference on Emerging Infectious Diseases.

“The current form of this virus remains highly pathogenic. If anything, it has become more pathogenic than it was when it first emerged in 1996 and 1997,” said Fukuda, acting director of the WHO global influenza program.

“H5N1 is not the only pandemic influenza threat out there, but it is by far the most visible threat, and because of that virus, there has been increased concern and action at the highest political level.”

The infection, which started in a goose in China in 1996, has been found in birds in Europe, including Croatia, Romania and Turkey. Avian influenza has also spread to Africa, Kazakhstan, Mongolia, Russia and the Ukraine. “There was a report of a large number of wild birds in Qinghai Lake in China, and when you go back to the viruses isolated in that episode, you can see that they were able to spread pretty successfully to many other parts of the world,” he said.

“In terms of human infections, the picture is somewhat more restrictive, with most of the infections still being identified in Asia, but important loci of infections are being reported in Turkey and Iraq, and we continue to have lot of infections ongoing in Indonesia right now,” Fukuda said.

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Response teams

WHO has mounted large response teams with experts from all over the globe who have been conducting investigations in “a number of unusual circumstances,” he said, showing a picture of epidemiologists in flak jackets in Iraq.

Public health officials have used two main global response strategies. The first addressed H5N1 as an immediate threat to agriculture, and revolved around culling the birds to stop the virus.

“But I think events over the past year have really shown this strategy, which is essential, has not been enough,” he said. “The initial approach when this really exploded in 2004 was based on surveillance, stamping out infected birds and quarantine as an effort to eradicate the virus from areas where it appeared.”

This has been a successful strategy in the West when other disease outbreaks have occurred on well-organized farms. It has not been as successful in Asia, he said. “Basically, it ran into Asia. It ran into the immense size of the H5N1 epizootic. This is no longer a small outbreak. It ran into the problem that much of the activity has occurred in small, unregulated flocks in impoverished, rural areas,” he said, and in countries that could not compensate people for killing their animals. “The impact on populations and economies has been considerable,” he said.

“This is a real problem if you want people to report disease activity in their neighborhoods,” he said. “In a lot of places, people really had to choose between food and disease control.”

Public health officials have modified that approach, and culling is more restricted. Some areas are using poultry vaccination, but there are a lot of questions about safety and efficacy.

The second strategy has been to implement pandemic preparedness activities, planning and coordination, surveillance and assessment, prevention and containment, he said.

There are other measures that can be implemented now, he said, such as increasing surveillance and developing stockpiles of antiviral drugs. Roche is increasing its capacity to manufacture oseltamivir (Tamiflu) and working with generic suppliers to make more medication.

“In the here and now, however, supplies continue to be limited,” he said.

WHO has recommended that countries develop a national stockpile, and at some point there may be regional stockpiles. WHO is building two stockpiles that will have a total of 5 million doses of antiviral.

Some researchers are trying to develop new vaccines. These include adjuvants to increase immune responses, and cell culture-based production methods. Some are looking at a universal vaccine, so that people would not require annual vaccination.

“The basic strategy for when person-to-person transmission is identified is that seasonal vaccine production will stop, and then pandemic vaccine will begin,” he said.

Companies can make 300 million doses of the seasonal trivalent vaccine. So, they probably could make 900 million doses of a monovalent vaccine, but there are 6 billion people in the world.

“Under the best of circumstances, it is still expected that it will take four to six months from the start of making the vaccine until it is ready,” he said. “Within six months it will have traveled pretty far.

“Are the current strategies enough? The answer is a clear no,” Fukuda said.

Public health officials must respond rapidly to contain the pandemic early: They must get ahead of the virus by having a plan in place, training local individuals to respond, stockpiling antiviral and educating citizens in infection control to prevent infections, such as telling children not to pick up dead birds.

“If you take decisive local action you can stop an outbreak,” he said, pointing to the SARS coordinated global response.

There are still daunting decisions to make, but the one that really keeps Fukuda up at night is equity. The vaccine is a case in point. There will not be enough vaccine for everyone, even in the best of circumstances.

“You are facing all countries in the world. How can resources be distributed fairly in the face of overwhelming demand,” he said. “This is such a difficult issue that I think this is the issue that most often has been pushed aside because it is daunting.”

Fukuda said it was time to address this issue, and an ethics conference is planned for June to look at some of the issues surrounding a pandemic influenza outbreak.

For more information:

• Fukuda K. Pandemic influenza and the global challenges. Opening keynote session. Presented at: 2006 International Conference on Emerging Infectious Diseases; March 19-22, 2006; Atlanta.