SACRAMENTO, Calif. – If the new swine flu spreading around North America with relatively few deaths so far is going to mutate into a mass killer, flu trackers expect to know by July.

That’s when flu season will be roaring through the Southern Hemisphere – providing breeding grounds for the ultimate influenza makeover.

From Sao Paulo to South Africa, every sniffling, sneezing human body will be an opportunity for the H1N1 flu to evolve.

Influenza, a slippery and elusive virus, is built to seize such opportunities – every time it replicates itself and every time it meets a different strain in some unhappy soul fighting two types of flu at once.

Knowing that change is a certainty, doctors and researchers worldwide are already on heightened alert, trying to gauge just how bad this one could become.

“We will just chase the virus and chase the cases,” said Dr. Nikki Shindo, medical officer at World Health Organization’s global influenza program. “We will be monitoring very closely how it spreads.”

Monitoring will happen in doctors’ offices, hospitals and sophisticated labs that can tease out genetic makeup of each new twist the virus takes.

Some of the work will involve basic sampling, trying to take enough random throat and nose swabs to learn how widely the flu is spreading. Epidemiologists sometimes talk about this as knowing the denominator.

Spurred by avian flu and SARS outbreaks, WHO, the Pan American Health Organization (PAHO) and the U.S. Centers for Disease Control and Prevention have been gradually building networks that could tease out the denominator as this H1N1 begins to hopscotch around Latin America.

“The really ironic thing is when we started this in PAHO, in the Americas, at the time everyone was thinking the pandemic would start in Asia,” said Dr. Anthony Mounts, an epidemiologist with the CDC’s influenza division.

This outbreak was first spotted in Mexico and Southern California, although researchers still don’t know where it began. Now it’s expected to spread worldwide, but because flu season is largely over in the Northern Hemisphere, early alerts about its changing menace are likely to come from the south.

Doctors and researchers will want to know not just how many people get the flu, but how many end up in emergency rooms, how many need to be treated in intensive care units and how many develop problems such as pneumonia.

Equally important, they’ll want to gather specimens from the desperately and the mildly ill, to begin looking for molecular changes.

Today at least a half-dozen South and Central American nations have large, well-equipped labs that can study whether the new flu is developing resistance to anti-viral medications or changing especially deadly bits of its genetic makeup, Mounts said.

If the flu becomes more dangerous, evidence will likely emerge from the numbers, with spikes in those seriously ill or dying. Laboratory details will follow quickly, said WHO’s Shindo, because samples from the sickest people will be prioritized, and the entire genome of a worrisome new variant could be sequenced in about a week.

Some of the twists researchers will be looking for: Will this flu pick up resistance to Tamiflu and Relenza, drugs that can knock it down now? Will its surface proteins shift so much that any vaccine we start developing now would be less effective by the time it’s deployed? Will it mingle with other strains that are quicker to kill?

“This virus loves to mate, probably as much as any other virus we’ve seen. It’s very promiscuous,” said Robert Webster, a virologist at St. Jude Children’s Research Hospital in Memphis, Tenn.

Initial changes are likely to move fastest in winter, when flu flourishes. A few cases of H1N1 have already been identified in Brazil and Argentina, but the Southern Hemisphere flu season gets under way in earnest in June and peaks in July or early August, depending on the location.

Virus experts like Webster and Dr. Andrew Pavia, who heads the pandemic flu task force for the Infectious Diseases Society of America, expect we’ll know by mid- to late July if this virus is becoming especially virulent.

Influenza viruses can change two ways. When two viruses infect the same person, they easily swap parts, exchanging one or more of their eight segments of RNA.

That’s a major change in basic equipment, like putting a new motor or alternator in a car, Pavia said.

Each time the virus replicates, though, it can make also make subtler changes, a little more like putting on a new coat of paint or a fake license plate, he said.

That steady antigen drift is part of why we need new flu vaccines regularly.

Whether the changes are big or small, what happens next is Darwinian evolution in action.

“Natural selection will favor … the changes in flu that make it spread better,” Pavia said. “If it causes a moderate increase in illness, if more people cough longer, it will spread more.”


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