Review
ATLANTA, March 20 - The genetic diversity of avian influenza viral strains with the potential to trigger a pandemic is steadily turning more menacing, researchers reported here today.
An analysis of more than 300 isolates of the highly pathogenic H5N1 avian flu, taken from both humans and birds between 2003 and 2005, shows that the virus is developing into two potentially dangerous genetic subgroups, said Rebecca Garten, Ph.D., of the CDC at the International Conference on Emerging Infectious Diseases here.
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- Advise patients who ask that the threat of avian influenza is so far confined mainly to birds. Human cases are rare and in most cases involve close contact with infected birds.
Note, however, that authorities fear the virus involved could evolve to develop efficient human-to-human transmission, which would create the potential for a pandemic.
This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
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"As the virus continues its geographic expansion, it is also undergoing genetic diversity expansion," Dr. Garten said in a statement. That increased genetic diversity means that the surveillance of the virus needs to be more intense, she said.
"Back in 2003 we only had one genetically distinct population of H5N1 with the potential to cause a human pandemic," Dr. Garten said. "Now we have two."
As the virus continues to spread among birds, Dr. Garten said she expects more diversity to evolve. "Change is the only constant," she said.
Currently, while millions of birds have been infected, only a handful of humans -- mainly those in close contact with poultry -- have been affected. As of March 13, the World Health Organization said, there have been 177 confirmed cases of H5N1 infection in people and 98 deaths.
Only a handful of those cases involve suspect human-to-human transmission. Nonetheless, the virus could become more efficient at spreading between people -- a change that authorities fear could cause a pandemic.
"Only time will tell whether the virus evolves or mutates in such a way that it can be transmitted from human to human efficiently," Dr. Garten said.
Dr. Garten and colleagues conducted a whole-genome phylogenetic analysis of their samples, both to distinguish what genotypes are circulating and to detect the re-assortment of genes that might cause a change in pathogenicity.
The main circulating virus is what's called genotype Z, Dr. Garten and colleagues said, but others are also in the mix, including genotype V and re-assorted virus of a mixed Z/W genotype.
The researchers also found considerable variation in the viral envelope protein hemagglutinin (HA) of the various isolates. HA -- the 'H' in H5N1 -- is known to be highly variable, even in normal annual flu outbreaks, and is medically relevant because it is involved in the virus' attachment to host cells.
The researchers found that the HA in their samples now falls into three distinct clades, or genetic subgroups, dubbed 1, 1', and 2. Clade 2 HA can be divided into at least six subclades -- dubbed 2A to 2F -- each with distinct amino acid patterns and the potential for different antigenic profiles.
Currently, Dr. Garten and colleagues reported:
The virus isolates found in Vietnam, Thailand, Malaysia, Cambodia and Laos are genotype Z, and have clade 1 HA; they have caused both human and avian disease.
Viruses with clade 2 HA and genotypes Z, V or Z/W re-assortants are responsible for the recent outbreaks of avian influenza in Indonesia, China, Japan, South Korea, Vietnam and Eastern Europe.
Importantly, the clade 2 HA viruses have been linked to human cases in Indonesia.
Until 2005, Dr. Garten pointed out, viruses with a clade 2 HA had not been known to infect humans.
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