Sometime in the last few years, as the world’s attention was focused on the bird flu that killed more than 250 people in Asia, another bird flu strain infected pigs.

FOR THE RECORD: A story in Monday’s Section A about the intricacies of the swine flu virus incorrectly stated that more than 250 people in Asia have died in recent years from the latest outbreak of bird flu. A total of 257 people have died, according to the World Health Organization, but only 222 of them were in Asia.

It mixed with two kinds of flu that are endemic in swine and a fourth that originally came from people.

The resulting concoction spread among pigs, then recently - no one yet knows where or when - started infecting humans. Since late March, it seems to have sickened people in California, Texas, New York, Kansas and Ohio, as well as in Canada and Mexico, where there have been 22 confirmed deaths.

Scientists said Sunday that they were unable to predict what this new swine flu would do next.

“It’s impossible to say with any assurance what’s going to happen,” said Dr. Christopher Olsen, a molecular virologist who studies swine flu at the University of Wisconsin School of Veterinary Medicine in Madison. “Influenza viruses can evolve quite quickly.”

Inspecting the virus itself is of little help, because scientists have yet to identify which features help it spread or kill, said Dr. Scott Layne, an epidemiologist at the UCLA School of Public Health.

“The microscope doesn’t tell you anything,” Layne said. “What are the genetic correlates of virulence? Unknown. Transmissibility? Unknown.”

The challenge of flu

Among threats to public health, influenza poses an unusual challenge. People, pigs, birds and horses have developed unique strains of flu, which can easily mix and match into new ones that the human immune system is ill-equipped to recognize.

And because the eight genes that form all Type A flu viruses - the most dangerous kind - are made of RNA instead of DNA, they don’t copy themselves reliably and are prone to further mutation.

Flu research has accelerated since the Asian bird flu spread to humans in 1997. But the more scientists study it, the more questions they have.

“I know less about influenza today than I did 10 years ago,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Yet for all its destructive power, the influenza virus is a straightforward organism.

Its outer shell is studded with a protein called hemagglutinin that allows flu particles to attach to cells lining the respiratory tract. The virus then takes over the host cell and uses it to make hundreds of copies. Those new flu particles use another surface protein, neuraminidase, to break off from the host so they can search for new targets.

There are 16 types of hemagglutinin, or H, and nine of neuraminidase, or N; the combination gives a flu strain its name. The swine flu involved in this outbreak is an H1N1 variety.

Scientists surmise that influenza originated in wild birds because they carry all types of H and N. Over thousands of years, the flu evolved into five major lineages, Olsen said - one each for humans, pigs and horses, and two for birds.

The swine strains

Swine flus were first detected in the 1930s, but pigs have probably had their own strains for hundreds of years, said Greg Gray, director of the Center for Emerging Infectious Diseases at the University of Iowa College of Public Health.

For a long time, swine flu was the suspected culprit in the 1918 Spanish flu pandemic that killed about 50 million people. Scientists now blame a bird flu strain, which probably infected pigs and humans simultaneously, Gray said.

The pandemics of 1957 and 1968 involved strains that contained a mixture of human and avian flu viruses. Experts theorize that pigs were the mixing vessel in those cases, “but there’s no smoking gun to indicate that,” Olsen said.

Swine flu infected 200 people in 1976, including four soldiers at Ft. Dix, N.J., one of whom died. The virus circulated for about a month, then vanished as mysteriously as it came, according to the U.S. Centers for Disease Control and Prevention in Atlanta.

In 1988, a healthy 32-year-old women who visited a pig exhibit at a county fair came down with pneumonia and died eight days later. Epidemiologists tested the exhibitors and found that 76% of them had swine flu antibodies, a sign that their immune systems had tangled with the virus, according to the CDC.

The agency typically reports a case of swine flu in humans once every year or two. But from December 2005 to February 2009, it documented 12 U.S. cases.

In the current outbreak, 20 people in the U.S. have contracted swine flu, along with six in Canada. Suspected cases have been reported in France, Spain, Israel and New Zealand.

Mexico is hardest hit: The government there has confirmed 22 deaths in patients with the virus, and a total of 103 deaths and 1,614 infections may be linked to swine flu.

Experts don’t know why the flu is more virulent south of the border. Perhaps the genetic code of the Mexican version is slightly different, Olsen said.

“It can take as little as a single amino acid change to have a substantial difference in pathogenicity,” he said.

Mexicans may have had longer exposure to the virus, and patients there may also be more vulnerable to secondary infections, such as pneumonia.

Cases go unreported

The World Health Organization estimates that swine flu is fatal in 1% to 4% of cases. But so many mild cases of infection go unreported that it’s impossible to know its true virulence, experts said.

In fact, it may not be all that rare. A 2007 study in the journal Emerging Infectious Diseases compared swine flu exposure in farmers, their spouses and a control group of university students, faculty and staff.

Compared with the control group, the farmers were 55 times more likely to have swine flu antibodies, and the spouses were 28 times more likely.

“There are probably a lot of infections that are totally missed from the medical system,” said Gray, who led the study.

Scientists are using samples of the new swine flu strain to infect laboratory animals, including mice, guinea pigs, ferrets and primates. Researchers will test whether direct contact is necessary for transmission and whether small flu droplets can spread easily from cage to cage. Those tests will provide clues about how easily the virus spreads and how deadly it is, Gray said.

“We don’t know what this virus will do,” Osterholm said. “It could burn itself out in the next four to six weeks and we never see it again. It could burn itself out over a more extended period of time.”

But he said health officials can’t ignore the chance that it could sputter out in the spring and reappear in late summer with a vengeance, as happened in 1918.

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2009 Los Angeles Times