September 17, 2009 The Pump Handle 0Comment

by revere, cross-posted from Effect Measure

I just got my seasonal flu shot. It was free and my medical center is encouraging everyone to get one. I wouldn’t be telling the truth if I said I didn’t feel it at all, but in all honesty, I hardly felt it. They must be using smaller needles these days. Anyway, given that most circulating flu virus is pandemic swine flu H1N1, for which a vaccine is not yet available (coming soon to a clinic near you, we’re told), you might wonder why I — or anyone –would bother. I’ll do my best to explain my reasoning, but I’ll grant at the outset I may have missed some good reasons or have reasons that are fallacious — you decide. The pandemic has produced lots of questions that don’t have easy answers. But I’ve been asked here a number of times what I was going to do and why, so I thought I’d give you an explanation.

As I’m sure all readers here know by now, the currently available flu vaccine is the usual seasonal trivalent vaccine (three components) designed to protect against circulating flu viruses influenza A/H1N1 (Brisbane), A/H3N2 (Brisbane) and influenza B (Victoria). Since flu virus changes every couple of years in ways that aren’t always predictable yet the vaccine has to be produced before we see what strains are actually circulating, there is always the risk of a mismatch — i.e., the prediction was wrong. That’s happened with one or another component of the vaccine a few times in recent years, although it’s thought that even mismatched vaccine gives some protection (the unhappy corollary is that even properly matched vaccines often fail to protect a significant fraction of vaccinees from infection; see our post about efficacy here). So how are we doing with matching this year?

Since the seasonal flu season hasn’t gotten underway in earnest (if indeed there will be one with seasonal subtypes), we don’t know yet, but the data up through week 35 (beginning of September), which is the most recent, shows the seasonal H1N1 is a complete match, that is, since October 1st of last year (the administrative start of CDC’s flu season), all of the seasonal flu A/H1N1 matched the vaccine component for this year, including up to last week. That’s a good sign that if seasonal H1N1 starts circulating again in earnest, the vaccination I got will give me maximum protection. In my age group (65+) it’s not clear how good that protection is. The immune systems of older folks doesn’t respond with the same alacrity as that of younger folks (as in many other things, alas), but if there’s seasonal H1N1 around like what we’re seeing now I’ve done the best I can as far as a vaccine goes. The news for the H3N2 and flu B components is not quite as good, although (so far) not terrible. The match over the last year for H3N2 is 93% and for flu B 89%. So these subtypes are changing and if both or either start circulating and change even more the vaccine won’t have done as well by me. But it will still have some efficacy — and potentially quite a bit — so I judged it netted out positively.

Let’s review for a moment what vaccine efficacy means. Really well matched vaccines can have efficacies of 70% or 80%. What that means is that if you compare the amount of influenza in a vaccinated group to an unvaccinated one, the amount of flu will be 70% (or 80%) less in the vaccinated group. That’s not complete protection, but it’s pretty good. Let’s be sure you understand exactly what this means. For clarity, let’s take 50% efficacy. This means that if you are exposed to enough flu virus that would have infected you without vaccination, your chance of actually getting the flu is now like a flip of the coin (50%). That sounds bad until you realize that the people you are being compared with people who aren’t vaccinated who are playing with a coin that has tails on both sides. I know which coin I’d rather play with.

But of course there’s more to it this year. We are in a very complicated situation, because the vaccine I got is thought to give me no protection against the virus that, at the moment, is the overwhelmingly predominant circulating influenza virus, the pandemic swine flu H1N1. The epidemiology of this virus is quite different from seasonal flu. For one thing it has been infecting people since April, straight through the summer, during a time when seasonal flu is normally at very low levels. Although we haven’t been doing surveillance during summer months since we didn’t think we had to (because we didn’t think there was any flu around), we could have been wrong that there’s hardly any flu in the summer. We just weren’t looking for it. But this year we have been doing virologic surveillance in the summer and it shows hardly any seasonal flu — 1 – 2% at most. So there are two possibilities. One is that seasonal flu is behaving as normal, and more or less disappears in the summer (that’s why flu is call “seasonal,” after all); or that it’s been there in other years and we’ve never looked for it but that this year pandemic swine flu has crowded it out of the host marketplace (however that happens). Either way, almost all the flu A virus that’s out there now is pandemic swine flu, the virus for which the vaccine I just got gives me no protection. So why did I get it?

Below is a graph I showed last week, from CDC’s FluView surveillance webpage. It’s the product of CDC’s Emerging Infections Program (EIP), a population-based surveillance network that monitors trends in laboratory-confirmed influenza-associated hospitalizations. The font is kind of small, so if you want to see the it full screen you can go here. What it is showing you is how the risk of winding up in the hospital with a lab confirmed case of influenza (any type or subtype) is shaping up since April, when the pandemic started. The horizontal dotted line in each panel is the average risk incurred in that age group over the last three flu seasons. Thus if this year is like the average of the last three years, you would expect the risk in your age group to rise to the level of the dotted line by the time the flu season is over. You can see that the risk is quite different this year for different age groups. I’m in the age group in the bottom panel (>65 years old):


The risk level is expressed on the vertical axis. For example, the number 2.0, the top value in the second panel, means that the risk of winding up in the hospital with a laboratory confirmed case of flu is 2/10,000 or 0.02%. It’s important to note that the scales in the top and the bottom panels are different than the four in the middle. Looking at these age groups what you see is the risks have ramped up most quickly in the 5 – 17 year old and 18 – 49 year old age groups, where the risk of hospitalization for lab confirmed flu has already reached or exceeded what it was at the end of the flu season, even though we are now at a time when we haven’t even started CDC’s official flu season. In the under 4 year old and the 50 to 64 year old groups, we’re already half way there, as well. In my age group, we’ve hardly budged. It looks like a normal seasonal flu picture, with risks just beginning to edge upward as fall is coming on. This confirms data from other surveillance activities that, for reasons that aren’t clear, the over 65 age group is being affected dramatically less than normal for flu. For swine flu deaths, my age groups is contributing perhaps 2% of the mortality, whereas for a normal (seasonal) flu season, the over 65 contribute about 90% of the deaths.

Remember, however, that I mentioned the difference in scales. CDC says (correctly) that the age group at highest risk is the under two year olds. If we look at the risks, we see why:

Rates for children aged 0-23 months, 2-4 years, and 5-17 years were 2.5, 1.0, and 0.8 per 10,000, respectively. Rates for adults aged 18-49 years, 50-64 years, and >= 65 years, the overall flu rates were 0.5, 0.6, and 0.5 per 10,000, respectively. (CDC FLuView, Influenza-associated hospitalizations)

What this says is that although the rates for children and adults ramped up much faster than the normal (low) rates, rates for my age group are so high that we are still about even, all somewhere around .5/10,000 people in our respective age groups, or 0.005%. Thus my risk of winding up in the hospital as a lab confirmed flu case is about the same as an adult over the age of 18. The risk for the under 2 year old age group is five times higher (2.5/10.000), which is why CDC says they are at greatest risk.

What I don’t know (and I don’t know if CDC knows either) is what is putting the 65+ group into the hospital at this moment. More to the point, I don’t know what will put my age group into the hospital as the flu season progresses. Here are the possibilities:

i. Pandemic swine flu A/H1N1 2009 almost completely replaces both subtypes of seasonal flu (seasonal H1N1 and seasonal H3N2) and there’s hardly any of it around. Then I get no or little benefit from getting vaccinated (except for the flu B part, which is significant). Since last week 2% of the isolates were seasonal flu, it’s hard to say what will happen. We don’t usually see much seasonal flu virus this early in the year anyway. Will the future be different?

ii. Pandemic flu and seasonal flu co-circulate. We don’t know if that can or will happen. But since I’m in the age group that dies from seasonal flu, I’ve done the right thing.

iii. Pandemic flu and seasonal flu are out of phase. For example pandemic flu has a sharp but short history and by virtue of using up susceptibles and vaccination it’s essentially gone by January, leaving an opening for the seasonal viruses to return and act as they usually do. Again, I’ve done the right thing.

iv. Pandemic flu changes character and starts to infect my age group, crowds out seasonal flu or something else. Depending on the nature of the changes (maybe it reassorts with something the vaccine works for) I might or might not have come out ahead and everyone else, of all age groups, might or might not come out ahead if they are vaccinated with the seasonal flu vaccine.

The truth is this. No one knows what’s going to happen. We’re all guessing. But in my estimation, the risk-benefit calculation for vaccine side-effects and flu is so markedly in favor of the vaccine that I made the decision to get vaccinated and that’s what I’d advise others, too. How confident am I? I’m confident it is the most rational thing to do given what we know. But flu confounds us at every turn, so being confident about anything else in this case is not something I’m confident about.

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