By Helen Branswell Medical Reporter (CP) – 4 hours ago
TORONTO — The World Health Organization's top flu scientist often describes the virus he's studied for years as "humbling."
And Dr. Keiji Fukuda isn't alone in marvelling at the mercurial nature of influenza. Flu scientists repeat almost as a mantra that the only thing predictable about flu is its unpredictability.
Yet despite decades of evidence that influenza will repeatedly rewrite the rules, flu dogma emerges and takes hold. Scientists keen to sift patterns from chaos agree X is true about Y - until the virus sets them straight yet again.
In the late '60s it was held that pandemic viruses emerged in 11-year cycles, after the closely spaced 1957 Asian flu and 1968 Hong Kong flu outbreaks.
It used to be accepted that only H1, H2 and H3 viruses could infect humans. And then viruses from the H5, H7 and H9 subtypes jumped from birds to infect people. Wrong again.
Though the world is not quite seven months into this pandemic, a number of widely held assumptions about flu and pandemics seem destined for the redrawing board when the dust from this outbreak settles.
Here are some:
-Pandemic viruses emerge from Asia, the cradle of flu viruses.
Years of focus on H5N1 avian influenza viruses left experts convinced Asia was the birthplace of new flu viruses and would be the source of the next pandemic. Despite the fact that there's good evidence the 1918 Spanish flu virus may have emerged in Kansas, no one was looking to North America as ground zero for the first pandemic of the 21st century.
It's a valuable lesson, says Dr. Nancy Cox, who has been pushing for a number of years for more flu surveillance in Latin America.
"You can't take your eye off the other possible threats. You can't focus too much on one area of the world because influenza - a new virus - can emerge from anywhere," says Cox, head of the influenza division at the U.S. Centers for Disease Control.
-Pandemics are triggered by "antigenic shift."
Flu viruses evolve constantly via small mutations, a process called antigenic drift. But once in a blue moon an entirely new virus bursts out of nature, an event known as antigenic shift. Because most people are vulnerable to the new virus, it ignites a pandemic.
It used to be thought pandemics could only be started by a virus with a new hemagglutinin - the H number in the virus's name - or a virus with a hemagglutinin that hadn't spread recently among people, such as the H2N2 viruses that circulated from 1957 to 1968.
The current pandemic is caused by an H1N1 virus, which is startling because almost everyone alive has antibodies to H1 viruses. They've been circulating among people since 1918, except for a 20-year gap between 1957 and 1977.
So few scientists would have predicted a new H1 virus could cause a pandemic at this point in history.
Some, in fact, still question whether this outbreak is a pandemic, at least by the definition science currently applies. The retired head of virology for the U.S. Centers for Disease Control is one of the doubters.
"There's no precedence for this," says Dr. Walter Dowdle, who now works for the non-profit Task Force on Global Health, based at Emory University in Atlanta. "Nobody had really thought that . . . the virus would re-emerge with this much background immunity."
But Dowdle cautions about dismissing the potential of this virus just because it defies our assumptions.
"We're the ones that make the definitions. And if the virus doesn't behave according to the definitions, well, it's our fault, not the virus's fault. So I think we have to be very careful about forcing the viruses into our definition, which can only be made based on what we've seen in the past.
Now we've seen something different. And so therefore we've got to go back and rethink this."
-Emerging pandemics can be extinguished with quick use of antiviral drugs.
Landmark modelling studies published in August 2005 suggested that with good surveillance, rapid response capacity and enough Tamiflu, a flu virus that was just starting to spread person-to-person could be snuffed out.
The late Dr. J.W. Lee, then director general of the WHO, committed the agency to try. Experts at the agency and elsewhere spent untold person-hours honing a plan for trying to stop a pandemic at source.
And while flu experts were watching the spread of H5N1 avian flu viruses from Asia, pigs got infected with some viruses that swapped genes and created the H1N1 virus we call swine flu. By the time we knew it was spreading, containment was out of the question.
"This cat was not only out of the bag, but this cat had nine litters before we realized what had happened," says Dr. Michael Osterholm, director of the University of Minnesota's Center for Infectious Diseases Research and Policy.
-We'd know it when we saw it.
Pandemics are rare. And before this one, only two had occurred in the era of virology. So what would a pandemic look like? Experts insisted it was a bit like pornography - we'd know it when we saw it.
And then a new virus of swine-avian-and-human genes started to spread.
It wasn't from a new subtype (see above). And but for the fact it was spreading in the off season and causing severe illness in younger people, it might have been mistaken for plain old flu.
Confusion ensued.
-There would be little time between the spotting of an emerging pandemic virus and the declaration of a pandemic.
The WHO's pandemic alert scale goes from Phase 1 (no threat) to Phase 6 (pandemic). For years the world had been at Phase 3, which means a non-human virus (H5N1) posed a pandemic threat and was triggering occasional cases, but person-to-person transmission was rare and limited.
Most experts assumed when a pandemic virus started to take off, the world would race through Phases 4 and 5 to 6.
Within 10 days of the first announcement that human swine flu infections had been found, the WHO raised the alert level from 3 to 4 and then to 5.
And then the world waited.
The virus spread as expected. What wasn't anticipated was political resistance to the declaration of a pandemic caused by such a mild strain.
The gap between Phase 5 and Phase 6 stretched for six weeks - not because of the virus, but because of political wrangling and perceived need to ease the world into the first pandemic in 41 years.
-A mutation at position 627 on the PB2 gene means trouble.
After years of study, flu scientists believe they've found a number of signature motifs in viruses that can predict characteristics like disease severity or transmissibility. One is a mutation at the 627 position on a gene called PB2.
For as far back as molecular biology can see, all flu viruses known to have spread among humans had the mutation. That has led flu scientists to peg it as essential to transmission in humans. But this virus doesn't have that mutation.
Flu virologists have been on the lookout for pandemic H1N1 viruses with this change, believing it would confer greater transmissibility and maybe greater severity of disease. But when it was found in a few cases in the Netherlands, there were no nightmare changes in the illness pattern.
-People would clamour for pandemic vaccine.
Much of the recent pandemic planning was done with H5N1 flu in mind.
The virus is a monster in humans, killing around 60 per cent of those infected. Planners assumed people would be desperate for pandemic vaccine.
But until recently, it seemed H1N1 wouldn't scare many people into vaccine queues. Instead, polls showed a surprising number were more nervous about the vaccine than the virus.
And even after the recent death of 13-year-old Evan Frustaglio of Toronto received widespread attention, a Canadian Press Harris-Decima poll showed only 55 per cent of Canadians want this vaccine.
Meanwhile in Europe, response to vaccination efforts has been indifferent.
"It's funny because I would not have predicted us to be in this situation a year ago. Because it's a no-brainer that you'll get the vaccine out and you'll want to vaccinate as many people as possible," says Dr. Michael Gardam, of the Ontario Agency for Health Protection and Promotion.
-People would need two shots of vaccine to be protected against a pandemic virus.
The assumption was that a pandemic virus would be so new our immune systems wouldn't be able to protect us against it with just one shot. One jab would be needed to "prime" our immune systems and a second to "boost."
Those assumptions were based on the idea a pandemic virus would be a new virus subtype, foreign to our immune systems.
Clinical trials of H1N1 vaccine show most people respond to a single shot of vaccine as if it's a booster, not a primer.
-Vaccine would be ready in time to combat the second wave of infections.
Planners expected more time between the emergence of the virus and a proper first wave of activity. And they thought there would be enough time before the second wave to make and deploy vaccine.
This virus has followed a different timetable, with a rapid and heavy first wave in the spring, continued activity over the summer and an early start to the flu season in the fall.
In Canada, the first supplies of vaccine have arrived as activity is really taking off in many parts of the country. Public health officials are in a race with the virus, trying to get vaccine into people before they can catch the bug. But it takes about 10 days for an immune response to develop after vaccination and in some cases, the virus is winning the race.
"I think most of us were hoping that there was going to be a longer gap between the initial identification and even a first wave," says Dr. Allison McGeer, head of infection control at Toronto's Mount Sinai Hospital.
The head of the CDC has been surprisingly blunt in his assessment of the existing system's capacity to make pandemic vaccine in a timely way.
"The technology we are using, although tried and true, is not well suited for pandemics," Dr. Tom Frieden has said.
-Hospitals would be crippled.
Pandemic planners thought hospitals would be overwhelmed. Emergency departments would be swamped. Overflow facilities might be needed. Surgeries would be cancelled.
No one knows what this winter has in store and that scenario could still materialize. Certainly after high profile cases like the Frustaglio death, emergency departments have reported heavy use.
But so far, hospitals haven't been overwhelmed - except intensive care units.
Severe cases of H1N1 are rare, but people who develop bad disease are profoundly ill. ICU staff have to take extraordinary measures to oxygenate the blood of these people because their embattled lungs cannot do the work for them.
ICUs in a number of hard hit places during the spring wave reported nearing the point of overflow. If they reach that point, experts say, death rates will rise and other hospital services will need to be rationed. But that hasn't been the case to date.
Follow Canadian Press Medical Writer Helen Branswell's flu updates on Twitter at CP-Branswell
Copyright © 2009 The Canadian Press. All rights reserved.
