Flu in view

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H1N1 Flu Virus. Creative Commons; Cybercobra at en.wikipedia

If there is one health care issue politicians in DC have managed to agree upon it is the importance of flu shots (although, where we get them and who pays is a different story.)  During flu season, whether in coffee shops, school cafeterias or online, everyone it seems, is an expert. We hear about who’s had shots, who’s gotten sick and how effective the vaccine really is (or isn’t). Some kids in my daughter’s school thought the vaccine could be lethal — really. Comb the web and you’ll find plenty of tragic and alarming mainstream stories and just as many discussions about the conspiracy of vaccination programs or comments like, “My co-workers all got the shot, and they’re all sick. I didn’t and I’m not sick. It’s obvious, the vaccine made them sick.”

True, vaccinated individuals may end up with the flu. If the barrista at my local shop  gets the flu post-vaccination it’s most likely because: the vaccine requires two weeks before it is fully effective; vaccines are not 100% effective; maybe she didn’t mount a strong immune response. The flu vaccine is the least likely cause of illness. And, aside from self-imposed isolation, vaccination is the only truly effective method of prevention.

Each year in the US the flu virus is associated with anywhere from 3,000 to upwards of 50,000 deaths, depending on the type of virus.  Recently, the CDC revised the estimated deaths associated with the 2009 H1N1 flu from 18,500 to hundreds of thousands, possibly half a million deaths worldwide.  The so-called Spanish flu pandemic of 1918 is believed to have taken 50 million lives worldwide. While the elderly are typically most vulnerable, the flu takes too many of our youngest, particularly infants who are more likely to be hospitalized.  In 2012-2013 there were 164 flu-associated pediatric deaths several were infants, one of them at my sister-in-law’s hospital in Allentown, PA.

Another blargument (as in blog argument) against vaccination is efficacy. As in, “I read the vaccine is only 60% effective, so why risk getting one?” It’s a reasonable question, so I asked Dr. Bernadette Albanese, college buddy and public health physician in Boulder, Colorado.

“That is 60% compared to ZERO [efficacy] if you do not get vaccinated,” she says. “Put another way, you can potentially prevent flu in well over half of a vaccinated population as compared to an unvaccinated population. When you have population size of 100,000 or 1,000,000 that adds up to a lot of people who will remain well instead of getting sick and spreading more disease.”

Unable to reproduce on their own viruses require living cells for replication, and flu virus is like a house-guest from hell. It enters uninvited, makes itself at home inside the nucleus where it takes over the cell’s reproductive machinery spawning hundreds of thousands or millions of near replica viruses which leave the cell in ruins upon their exit.  This wholesale destruction tends to occur along the respiratory tract – which is why those of us with asthma or other respiratory problems are at greater risk for complications.

We are asked to submit to vaccines once a year in large part because flu viruses evolve rapidly.  Replication is never perfect. Mutations happen and with millions of progeny a good mutation can spread quickly throughout a viral population. Next year’s flu is seldom the same as this year’s or even last year’s. This kind of antigenic drift is why a different vaccine is required each year. And Influenza A, a primary cause of seasonal flu also has another evolutionary trick. Rather than simply drifting a virus might undergo what’s called an antigenic shift. Made up of eight RNA segments, influenza A can behave like a stack of Legos swapping out one block or segment for another and it can do this with flu viruses that infect animals other than humans. Should a human flu virus find itself sharing a cell with a pig flu or duck flu we might face a highly lethal pandemic flu for which humanity is ill-prepared, much like the flu of 1918.

Influenza quarantine camp set up at Wallangarra, 1919; Wikimedia Commons; Public Domain.

So, if viruses like flu evolve so rapidly, why didn’t they wipe us out in the pre-vaccine days when they had the chance?

There several books and articles on the topic, but here are two interesting articles discussing the ongoing arms race between proteins called host restriction factors that can block virus replication thereby putting the brakes on infection, and viruses. The first, “Evolutionary conflicts between viruses and restriction factors shape immunity,” by Nisha Duggal and Michael Emerman, explores our ongoing relationship with viruses. And given how quickly they evolve – it’s not all good.

The bad news according to the Duggal and Emerman is that:

“…our immune responses to contemporary viruses have been shaped by our evolutionary responses to previous infections. The modern innate immune system is generally not yet optimized against modern viruses, but rather was selected for by previous rounds…”

But they also write, “by determining the types of viral infection that occurred in the past and how they were eliminated, we can form new ideas about how to manipulate the immune system to our advantage…” (Just another nugget for those of us who insist that understanding the past can help prepare us for the future – or at least the present.)

We’ve managed to hold our own, in part suggest Duggal and Emerman (and this is the good news) because 1) we maintain polymorphic restriction factors, or variation within the population, which, on a short time-scale “force a virus to evolve the ability to target multiple alleles of a given host factor,” sort of like putting our eggs in many different baskets and challenging the virus to find them 2) we undergo gene duplication which in turns allows for more genetic innovation and 3) we benefit from the evolutionary constraints that are imposed upon certain viruses, particularly RNA viruses that rely upon overlapping reading frames and proteins with multiple functions. Evolution in other words even in rapidly evolving organisms can only take them so far.

Another interesting article is by Nicholas Meyerson and Sara Sawyer, “Two-stepping through time: mammals and viruses”  focuses on the constraints, suggesting a cyclic kind of arms race where both host and virus re-sample from “a small number of biochemical forms.” Genes coding for proteins which continuously cycle through a limited set of mutations might be selected in a sort of “rock-paper-scissors” dynamic. Such a constrained set of options could help better predict influenza evolution.  However, they note, playing the game requires that options arise through point mutations only (one DNA-base change at a time), rather than re-assortment or recombination both of which occur often enough, particularly for viruses like the flu.


Influenza Virus Vaccine, Photo Credit: Jim Gathany for CDC.

That we are endowed with an adequate immune system provides more ammunition for those wary of seasonal influenza vaccines. Every flu season brings its share of articles touting our natural defenses. We are strong. Why bother with vaccines? It is true that viruses and our ancestors have been engaged in mortal combat since their earliest existence. But, as any high school student ought to be able to remind us, evolution does not apply to individuals but to populations. So the argument that humans and viruses have co-evolved is all well and good – if we are only concerned with the survival and fitness of human populations.  But we recall that there is plenty of variation for any trait within a given human population. The argument falls apart when we value each and every member of society. Some of us are certainly more susceptible to the flu than others. And so we return to the question of vaccines.

“Vaccination is a choice and each person makes a decision to reduce their risk of disease or take their chances,” emailed Dr. Albanese. “That would be fine if when you get sick the only person affected is just you. But that’s not how it is because people get flu and move around plenty. They go to work, school, child care, malls, theaters, restaurants and the like. PEOPLE SICK WITH THE FLU GET OTHER PEOPLE SICK. The problem is that often, protection of others is not what one considers when weighing the decision about vaccination. You might only think about your own risk and how worried you are about having fever, body aches, or cough. People do not realize that their illness could have spread to a little baby, or an elderly person, or someone with cancer.”

Sometimes it’s not just me or you.

This post has been submitted to the NESCENT Blog contest!

For more about flu see http://www.cdc.gov/flu/; there are excellent maps tracking flu.

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