Some facts on the ‘Flu

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Canada’s not just gripped by crazy weather right now. Between a thousand cases of H1N1 swine flu (with ten deaths) in Alberta, and the first North American death from H5N1 avian flu, some Canadians are wondering if this is the start of Outbreak or Contagion, albeit more polite.

Used under a creative commons license via Flickr

I asked a friend (let’s call him Dr. F)—who is also an infectious disease specialist, to give me some facts. He’s amazingly good at explaining complex things easily, and his responses to my questions were simply too good not to share.

Before that, a quick backgrounder on viruses (mine, not his.) These tiny creatures cause a lot of diseases, from flu to ebola, and our bodies fight each version of each virus with a specific antibody. It’s a tiny version of rock, paper, scissors: if the virus is a rock, we make a paper antibody in return.

The problem is, sometimes the viruses overwhelm us before we can make antibodies to fight them off. Vaccination fixes this by teaching our body how to fight ahead of time, using a weakened version of the virus.

This is like getting in a boxing ring to spar with a non-lethal opponent, so you’re ready to defend yourself when you get mugged. Only in this case, each mugger has a name (H1N1, for example) and you need a sparring partner who fights just like that mugger (an H1N1 vaccine.)

Oh, and the muggers are always trying out new moves, and sometimes they share tips. But more on that below.

Influenza virus by Sanofi Pasteur

AC: The possibility of H5N1 avian flu spreading scares the shit out of me. It makes me think of the Spanish Flu, which killed 3-5% of the world’s population—and back then we didn’t have air travel to help spread it!

Dr. F: This is so right up my alley, AC (can I call you AC?) that by the end of this you may regret you asked.

Influenza is a fantastic example of evolution happening right in front of our eyes.

First things first, respect this enemy. I’m absolutely there with you in terms of panic level. This brainless virus is so stupid, it’s brilliant (explained below).

Every time an influenza virus replicates—which is estimated at 1 billion times a day—it plays Russian roulette with its genes (something called Antigenic Drift / Shift; videos here and here if interested.)

It’s the roll of the dice that eventually will land on the right combination and produce a brand new strain of the flu virus never before seen by a human. This novelty means that no human is, therefore, protected by already-present antibodies. This is an incredibly dumb way to reproduce, actually. The overwhelming majority of these “gene switches” result in weakened viruses that cannot survive or replicate. But in a game of chance, all it takes is “once,” which has actually been calculated (I think it’s around every few decades).

Now Antigenic Drift is like “mini” changes and even though new strains pop out, we still have “some” immunity. Antigenic Shift is when a brand new virus (like the recent H7N9) develops and has potential for a pandemic.

The recipe for a pandemic is basically this:

  1. Russian roulette until there’s a major shift (Antigenic Shift) to a brand new virus that is viable and capable.
  2. The ability to transmit from person-to-person.
  3. A high transmission rate, meaning the virus needs to be able to easily jump from one person to the next. This is best encapsulated by one of my favorite statistical metrics, R0 (R-naught,) which is a mathematical model of how many people one person will infect). So, for influenza, R0 is about 2 (every person is responsible for passing it on to roughly 2 people). For H1N1 in 2009, it was less… around 1.8. That’s not too much of a scary number amongst viruses, actually. But, it’s scary enough.

The only way to stop the wildfire of a pandemic due to a brand new strain is the development of a vaccine. In the Spanish Flu cases of 1918, it took about 8-9 months to develop a vaccine.

Until recently, there was no push to advance vaccine technology (which was decades old). New, faster methods are in the works.

I should also mention that the only drugs we have for the flu (like Tamiflu) have limited efficacy. Even with the best use of these drugs, they only go so far.

This is due at least in part to another interesting facet of Influenza: Although the virus itself damages the host, in more severe cases, there is thought to be large part played by the host’s own overly-aggressive immune response.

Imagine that an enemy has infiltrated the castle walls (the lungs, in this case). Instead of sending immune “snipers” to take a clean shot at Influenza, our bodies seem to sometimes prefer sending immune missiles. Yes, missiles will kill the virus—but they cause significant collateral damage to our very own castles, too: Bad virus. Mediocre drug. Raging immune response, potentially doing more harm.

Logically, then, it follows that prevention with vaccines are incredibly important and vaccine-avert people like Jenny McCarthy do tangible harm by spreading fallacies (see the Jenny McCarthy Body Count).

So, now let’s use the background we’ve set above and transfer it to H5N1 (which just 2 weeks ago made its unwelcome entrance to Canada).

The most disturbing thing about H5N1 is that the mortality rate is ridiculously high (over 50% vs the H1N1 which was estimated at less than 10% in hospitalized patients in 2009.)

But a few significant differences are noteworthy and cast more than a silver lining (for now):

  1. The virus has been around since 1997 (though probably in slight different “forms” thanks to slow Antigenic Shifts). So…
  2. There are vaccines for it already (though not included in the typical flu vaccine because H5N1 is so rare).
  3. The R0 is essentially zero because there has not been a proven case of transmission from person to person. It’s all been from poultry (and maybe pigs.)

That being said, if H5N1’s 1 Billion dice rolls tomorrow make it so that it’s able to transmit from person to person… then Uh-Oh! Although remember, we are still ahead of the game with vaccines that are at least marginally protective.

Another point: The high mortality rate is actually an evolutionary disadvantage. If you (the virus) kill your host (the human) too often or too quickly (as Ebola does), then you can’t be passed along and survive in the world as effectively.

In other words: I hope you all got your flu vaccines!

Respect the flu. Otherwise-healthy adults die from the flu—as is being reported already in Los Angeles County.  Sadly, in one of our fatal cases this season, the family had tried to encourage the patient for years to get the vaccine.

AC: Does the emergence of new viri (sp?) come from combination, or just dice? For example, is the proximity of H1N1 (in Alberta) and H5N1 likely to create a virus with the mortality of bird flu (60 percent) and the R0 of H1N1? Or is it just up to the two of them to roll the dice separately?

Dr. F: Your thought is more in line with how the genes of these viruses re-combine. I was simplifying with the dice rolling.

For one strain of virus (ie, H1N1) to slightly change via antigenic drift, it doesn’t need any buddies. But, like that video for antigenic drift implies, when two or more virus buddies are around, they start exchanging genes, in essence “teaching” each other their tricks.

So, yeah, exactly right… say H1N1 and H5N1 infected the same animal and H1N1 “taught” H5N1 how to transmit from person to person. That would be a genetic coup for H5N1 because it just got one step closer to going pandemic.

AC: Is there a push to increase the number of strains in the annual vaccine? What is the downside of, say, including all known strains in the vaccine?

Dr. F: The vaccine studies are gaining some fascinating steam. There are cost, production, and efficacy limitations to including many strains in the same vaccine. Smart people decide the most likely circulating strains and choose to make those vaccines. They are remarkably accurate—though sometimes they miss.

This year, for the first time, vaccines with four strains (rather than the standard 3) are being utilized. I think with proven success over time, the strain inclusion will go up (but likely will not include the rarer and “scarier” strains).

The most interesting research is in developing a universal flu vaccine. There is hope for finding (I think a few have already been found actually) a viral target common to all influenza viruses (all flu A and flu B strains) that will effectively do what you suggest: protect us against any/all influenza. Early trials, I believe, are under way.

There are also attempts to develop a vaccine that will provide lasting immunity beyond just the few months that the current vaccines provide. My guess is that in our lifetime, we will likely see the day where you get one last flu shot and you’ll be protected for the rest of your life.

AC: I know you said host mortality was an advantage, but if I remember what my dad told me about parasites, doesn’t that depend on the rate of transmission, the period of incubation and the vector of transmission (I.e. Ebola and spraying fluids all over the place as you die)? If the guy made it from a bird, to an airport, to Canada before dying, and it were contagious, he’d have filled a plane of people?

Dr. F: You’re exactly right about the mortality issue. There is more than just one factor involved.

Case in point: the Canadian H5N1. The virus is “smart” enough not to have made the patient sick too fast, allowing them to travel back to a land the virus hasn’t yet seen. Essentially, somewhat of a survival of the “fittest.” And for a virus, “fittest” means being able to find a stable host, a stable energy supply, and replicate as much as possible by infecting more and more hosts with just the transmission rate and incubation time.

And certainly the ability to travel is important. Gaëtan Dugas is a name you may be familiar with. He’s the alleged patient zero in the HIV epidemic in the 1980s… and you know what he did for a living?

He was a flight attendant for (gasp) Air Canada.