As bird flu mutates, scientists worry, page 1

WASHINGTON - Like the rumble of distant thunder, bird flu continues to spread across Asia, Africa and Europe. Although it's been out of the news lately in the United States, scientists say avian influenza, as it's also known, remains a serious threat to human and animal health.

The lethal H5N1 version of the virus is mutating rapidly and rampaging through bird flocks throughout those parts of the world, infecting and often killing people who come in contact with them.

The fear is the virus will change into a form that makes human-to-human transmission quick and easy. At least seven slightly different subtypes already have been identified.

"New genes are being formed all the time," said Henry Niman, a molecular geneticist who tracks bird flu outbreaks around the world.

Although H5N1 hasn't reached the Western Hemisphere, Joseph Domenech, the chief veterinary officer for the U.N. Food and Agriculture Organization, warned in January that it "could still trigger a human influenza pandemic." A pandemic is a worldwide outbreak such as the 1918 Spanish flu, which killed tens of millions of people in the United States and Europe.

The virus "continues to cause human disease with high mortality and to pose the threat of a pandemic," the latest situation report from the World Health Organization says.

As of Feb. 20, bird flu had infected 362 people and killed 228 of them in 14 countries in Asia, Africa and Europe.

In the past year, the WHO confirmed 98 new human cases, including 69 deaths, an alarming 70 percent death rate. It was the second-worst year for bird flu, topped only by 2006, when 115 cases and 79 deaths (69 percent) were reported.

Since the major outbreak in China in 2003, the virus has killed millions of chickens, ducks and geese along with pigs, cats and other mammals in some 50 countries.

Almost all of the people who've been infected caught the disease from close contact with domestic poultry and occasionally from wild ducks, geese or swans. In a handful of cases, scientists think the virus passed from one human to another, usually among relatives or people living close together.

"So far, the spread of H5N1 from person to person has been very rare," the U.S. Centers for Disease Control and Prevention reported.

For example, eight family members in Indonesia caught the disease in 2005, and all but one of them died. A pregnant Chinese woman passed the virus to her 4-month-old fetus last fall. Both died. Four brothers in Pakistan were infected last winter, and two of them died.

"It's pretty clear that was a case of human-to-human transmission," said Niman, founder of Recombinomics, a genetics research firm in Pittsburgh.

Multiple teams of researchers are studying the details of how the virus performs its deadly work. They hope their findings will lead to better vaccines to limit or prevent infection, but the problem is difficult.

Vaccines such as Tamiflu that are used for common seasonal flu offer partial but not complete protection from H5N1. Furthermore, the virus already is developing resistance to these vaccines.

Recent research has discovered several reasons that human-to-human transmission of H5N1 has been limited so far.

For one thing, bird and human viruses have different shapes, according to Ram Sasisekharan, a biological engineer at the Massachusetts Institute of Technology in Cambridge.

To cause infection, the virus must fit a spike on its surface, known as HA, into a hollow "receptor" on the surface of a human cell. The virus that attacks birds fits its HA spike into a cone-shaped receptor. To infect humans, however, the spike must fit into a slightly wider receptor shaped like an open umbrella, Sasisekharan said.

"For animal influenza viruses to cause pandemics in human population, their HA protein must acquire mutations that allow human-to-human transmission," Carole Bewley, a biochemist at the National Institutes of Health in Bethesda, Md., noted in the January issue of the journal Nature Biotechnology.

"Fortunately, this barrier has so far protected us from rapid spread of H5N1."

Eight family members in Indonesia caught the disease in 2005, and all but one of them died.