Scientists find human barrier that limits spread of bird flu
Disease would have to mutate several times to trigger pandemic, they say
By SUSANNE RUST
srust@journalsentinel.com
Posted: March 22, 2006
An international team of researchers, led by University of Wisconsin-Madison flu expert Yoshihiro Kawaoka, has identified the biological roadblock that prevents the avian influenza virus, H5N1, from transmitting easily between people.
Researchers familiar with the study, published today in the journal Nature, say the findings are "comforting" because they indicate that it may be difficult for the disease to become the deadly human pandemic many have feared.
"This paper gets better every time I read it," said William Schaffner, a flu expert and head of the preventive medicine department at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved in the study. "They combined modern immunochemistry with old-fashioned anatomical reasons for explaining why certain diseases spread and why some don't."
Since 2003, more than 100 people worldwide have died from H5N1. Most of these people have had close contact with infected poultry. However, the disease has not been able to jump easily between people. And although there are a handful of purported human-to-human cases, these have been among family members and caregivers who were in close contact with the sick.
To understand why it's been so difficult for H5N1 to spread between people, Kawaoka and his colleagues asked the question: What are the molecular barriers that limit this transmission?
To answer that, they examined cells on tissue samples taken from the respiratory tracts of eight people. They were looking for specific receptors - or surface molecules - that are known to bind to H5N1 influenza viruses.
They discovered that only cells located in the deep, dark recesses of the human lower respiratory tract could bind to avian flu. Those in the upper respiratory tract, where human flus are carried, could not.
Human flus, which can be contracted through the air, generally move between people by catching a ride on the currents of sneezes and coughs. But because the avian flu is lodged so deeply in the lungs, once it's in, the virus has a difficult time climbing back out.
The finding may also explain why the disease manifests itself as a deadly pneumonia, Schaffner said.
He said that while the vast majority of human flus begin as bronchitis, with pneumonia occurring only as a result of "the bacterial wreckage" caused by those upper infections, the avian flu goes directly to the lungs, causing a pneumonia that is viral in origin.
"This study explains why we're seeing what we're seeing," said Dennis Maki, an infectious disease expert at UW-Madison, who was not involved in the study.
But, he said, it shows something else, too - something that could bring people hope.
"Two hundred to 300 million birds have been infected" by the disease, Maki said. And probably "about a billion people have been in very close and daily contact with these infected birds."
Despite the ample exposure and opportunity, the virus has not yet become an efficient human killer.
"Could it happen still?" he asked. "Yes, absolutely."
But the research indicates it's going to take a lot more than a single mutation, as some have predicted, to get this virus to become the human killer many have feared, he said.
Indeed, Kawaoka and his colleagues note in their paper that for H5N1 to become an efficient human-to-human traveler, it'll need to undergo a series of key genetic mutations.
This could buy time for health officials to prepare for a future pandemic, whether it's via H5N1 or another new strain.
But Maki is hoping the disease will burn out in birds before it ever begins to spread efficiently between people.
To speed this process, he said, "we may want to selectively immunize domestic poultry, as the Chinese and Europeans are planning to do, to prevent transmission from infected domestic birds to people.
Then, the risk of transmission would mainly be from infected wild birds that can spread the disease - a reservoir with which people generally have very little contact.
He added that if people start to see H5N1 disease in wild North American birds, we should not only keep all domestic fowl indoors, but also pet cats, "because cats are easily infected and could pose a risk to humans."
From the March 23, 2006 editions of the Milwaukee Journal Sentinel
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