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H1N1(Swine Flu): Influenza…A Humbling Virus – And Always, Always Unpredictable

November 12, 2009

Most people don’t really understand the nature of influenza…I mean after all, it is only the flu!  But that is exactly the problem; it is the flu!  As is now being played out on the world stage, influenza continues to show that it is in charge and is always, always unpredictable.  WHO’s top flu scientist Dr. Keiji Fukuda, often describes the virus he’s studied for years as “humbling.” And he is not the only one who marvels at the disease. Like a mantra, flu scientists repeat almost the only thing predictable about flu is its unpredictability.

In spite of this, myths begin to take hold and people begin to think that they really understand and have “figured out” the virus. Everyone is trying to find the pattern that will show predictability. 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. And then 41 years passed. 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.

Helen Branswell the award winning Canadian Medical Reporter has pulled together the current flu assumptions that are being redrawn seven months into our current pandemic. 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.
Lawrence, Mass 1918

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.

  • 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.

  • Emerging pandemics can be extinguished with quick use of antiviral drugs. Landmark modeling 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. 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. Did I mention we were confused?
  • 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.
nm1141-F5

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 clamor 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.
immunizations_photo1

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.

  • 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. 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.
  • 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. 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 has 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.
tabletop-book-style-flip-scoreboard

So what is the net-net to all of this…we think we know a lot but in reality we still don’t know much about this foe known as influenza! The score stands at Influenza 1 and Humans 0.

http://www.google.com/hostednews/canadianpress/article/ALeqM5gQJKPs4cD29K5qHQFiM3q5sYUI

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