US Nosts Bird Flu Meeting for 65 Nations

U.S. State Department Hosts Bird Flu Meeting for 65 Nations

Scientists report discoveries in bird flu and more common strains

By Cheryl Pellerin
Washington File Staff Writer

Washington – In response to a growing number of human deaths from bird flu and the fear of a pandemic, the U.S. State Department is hosting a two-day meeting of officials from more than 65 nations and international organizations concerned about preventing the spread of an influenza virus that has stricken birds in 11 nations.

Under Secretary of State Paula Dobriansky and Department of Health and Human Services Secretary Michael Leavitt will open the International Partnership on Avian and Pandemic Influenza Senior Officials Meeting October 6 at the National Academy of Sciences in Washington.

The meeting’s main objective is to affirm the commitment of participating countries to work together to fight avian influenza and jointly develop a plan of action to supplement international efforts.

State Department spokesman Sean McCormack said October 5 the agency hopes all participating countries will support a set of core principles that Dobriansky and Leavitt unveiled at the United Nations in September.

“At the heart of these core principles,” McCormack said, “are quick and accurate reporting of potential outbreaks, donor support for countries that have been or might be affected, and a pledge to work closely on the issue with the World Health Organization (WHO).

“This is just one more step that our government as a whole is taking,” he added, to ensure an effective response worldwide in the event of an outbreak.

At U.N. headquarters in New York September 29, Secretary-General Kofi Annan appointed Dr. David Nabarro coordinator for avian and human influenza.

Nabarro will be responsible for ensuring that the U.N. system makes an effective and coordinated contribution to the global effort to control the bird flu epidemic.

WHO has confirmed 116 human cases of bird flu and 60 deaths since December 2003. Only Vietnam, Thailand, Cambodia and Indonesia have reported human cases of the disease caused by the H5N1 virus subtype, which has resulted in the deaths of an estimated 150 million birds.

DISEASES FROM ANIMALS

Bird flu is just one disease that has arisen in animals and mutated to infect people. HIV/AIDS, severe acute respiratory syndrome (SARS), West Nile virus and the Spanish flu of 1918, which is closely related to avian flu, are just a few examples.

The 1918 Spanish flu was a global disaster, killing 20 million to 50 million people, many of them otherwise healthy adults.

Now, researchers partially have reconstructed the Spanish flu virus and discovered in part what made the virus so lethal. Such information is essential for influenza drug and vaccine research.

The research, published in the October 7 issue of the journal Science, says the Spanish flu virus is related more closely to avian flu viruses than other human flu viruses.

Many experts say it is only a matter of time before an avian flu outbreak occurs in humans and develops into a global pandemic, potentially taking millions of lives.

Therapies against a new flu strain would need to disarm parts of the virus that are most damaging to the body.

RECREATING SPANISH FLU

To learn which virus components would be the best targets for therapies, Terrence Tumpey of the U.S. Centers for Disease Control and Prevention (CDC) and colleagues recreated the 1918 Spanish flu virus.

Using the virus' genome sequence, Tumpey's group created a live virus with all eight of the Spanish flu viral genes. The genome sequence information was recovered in fragments from lung autopsies and lung tissues from a flu victim who was buried in the Alaskan permafrost in 1918.

The virus is contained at CDC, following stringent safety conditions designed for flu viruses and heightened security elements mandated by the CDC's Select Agent program.

"We felt we had to recreate the virus and run these experiments to understand the biological properties that made the 1918 virus so exceptionally deadly,” Tumpey said.

“We wanted to identify the specific genes responsible for its virulence,” he added, “with the hope of designing anti-virals or other interventions that would work against virulent pandemic or epidemic influenza viruses."

To make the virus, the researchers used an approach called reverse genetics, which involves transferring gene sequences of viral RNA into bacteria and then inserting combinations of the genes – often after manipulating them – into cell lines, where they combine to form a virus.

Like DNA, RNA is a nucleic acid. One of its main functions is to copy genetic information from DNA and translate the information into proteins.

The researchers, who included Jeffery Taubenberger of the U.S. Armed Forces Institute of Pathology, also produced variations of the virus for comparison, replacing certain Spanish flu genes with corresponding genes from other flu viruses.

They then studied the viruses' effects in mice, chick embryos and human lung cells, and identified the genes responsible for the Spanish flu virus's extreme virulence.

More research is needed on anti-virals and vaccines for a future flu pandemic, but Tumpey noted encouraging signs.

The FDA-approved flu anti-viral drugs oseltamivir (Tamiflu®) and amantadine (Symmetrel®) have been shown to be effective against viruses carrying certain genes from the Spanish flu virus. And vaccines containing other Spanish flu genes were protective in mice.

FLU VIRUS 101

Influenza A and B are the two kinds of flu viruses that cause epidemic human disease. Since 1977, according to the CDC, influenza A (H1N1 and H3N2) and influenza B viruses have been in global circulation.

In 2001, H1N2 viruses (probably a combination of H3N2 and H1N1) began circulating widely. Bird flu subtype H5N1 is an influenza A virus. Influenza A is a constantly mutating virus; influenza B does not mutate as rapidly.

Two kinds of vaccines protect against the influenza A and B strains that sweep populations during the winter months.

Each vaccine contains three flu viruses, representing one of the three groups of viruses that circulate among people in a given year.

Each of the three vaccine strains in both vaccines – one A (H3N2) virus, one A (H1N1) virus and one B virus – represent flu vaccine strains that flu experts think will be the dominant strains that year.

The yearly flu shot prepared and administered in the United States is an inactivated vaccine (containing killed virus) that is given with a needle, usually in the arm. The nasal-spray flu vaccine contains attenuated (weakened) live viruses and is sprayed into the nose.

The flu experts formulate their recommendations for the composition of the vaccine each year after much research and some guesswork.

SEQUENCING THE FLU GENOME

At the University of Maryland, Steven Salzberg and co-authors reported in the journal Nature October 5 that they had performed the first large-scale sequencing of 209 complete genomes of influenza A.

It is a technique the authors think significantly can reduce the guesswork scientists have had to rely on to predict which virus will emerge as the dominant starin in approaching flu seasons.

"This is the first-ever large-scale project to sequence the influenza virus," Salzberg said. "It is already giving us remarkable new insights into the rapid evolution of the flu as it moves through the human population."

The initial results are for the Influenza Genome Sequencing Project, a joint project of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and several scientific partners, to help researchers understand how flu viruses evolve, spread and cause disease.

Until now, viruses have been analyzed using an imprecise technique that cannot keep track of influenza A's rapid genetic changes – a viral survival skill that makes it difficult for scientists to prepare an effective vaccine for coming flu seasons.

FLU SURVEILLANCE

"Our sequencing project will help create a new, far more detailed surveillance system for the flu, to help decide which vaccine will be the right one from year to year," Salzberg said. “It promises to give us a more comprehensive picture of the pattern of transmission through human and animal populations."

The ability of influenza A to mutate its genetic code makes it dangerous. The virus mutates from year to year, making it necessary to update flu vaccines annually.

Less frequently, but with deadly results, the virus goes through a major change called an antigenic shift that creates new strains to which humans have no immunity.

This happens when two distinct flu strains exchange genes and is especially deadly when the exchange occurs between human and bird flu. The result can be a worldwide pandemic.

"Our sequencing project will help create a new, far more detailed surveillance system for the flu, to help decide which vaccine will be the right one each year," said Salzberg.

The result will be a more comprehensive picture of the pattern of transmission through human and animal populations, he said.

"The goal,” Salzberg added, “is to sequence thousands of influenza genomes, including avian influenza. By making the data public immediately, we can speed up the process of understanding how the virus is mutating all over the world."

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