Edit: I’ve updated the table to reflect the CDC’s numbers for age distribution of infection, which I didn’t see first time around. Thanks to Marcello Pucciarelli for the link. The original version of this post, containing my guesswork on the distribution, is still available here. Using the more accurate numbers has very little effect on my overall conclusions.
I’ve been expecting a resurgence of swine-origin influenza virus (SOIV) in North America for a while now, and it hasn’t happened. The virus is still out there, still infecting a few thousand people per week, but there hasn’t been a third large-scale wave of virus transmission. That’s different from the 1918 and 1957 pandemics (see here for details). What’s different this year?
Of course there are tons of things that are different this year, but I recently got around to doing something I should have done a while ago: Trying to estimate what proportion of Americans are now immune to SOIV. I’ve seen estimates that around 40% of the population should now be immune. I get roughly the same number (slightly higher, closer to 50%, because those estimates didn’t take into account pre-existing immunity to SOIV), but I think there’s an important point that might be missed in this: Most of the immunity might be clustered in the two most susceptible populations (children and the elderly), with two-thirds to three-quarters of them being immune.
There are three ways someone could be immune to SOIV. They could have been exposed to a related virus, some time in the past, and have developed a long-term immunity. They could have been infected with SOIV, somewhere in the first or second wave. Or, of course, they could have been vaccinated.
Numbers for each of those are available. They’re more or less approximate; not all the sources break down age groups in exactly the same way, for one thing, and I don’t have precise numbers for everything.1 I’ll try to flag places where I’m especially guessing, and it’s entirely possible that this I’ve made some obvious, basic mistakes in here, since this has been written in the interstices of cleaning our house for Chinese New Year (a Herculean task) and hosing down the kids to get them ready for the party at YongHui’s this evening. If so, let me know and I’ll try to correct them.
We need to break immunity down by age, because pre-existing immunity to SOIV was strongly age-dependent. (That’s presumably why the virus was strongly biased to infecting younger people this year.) For the demographics of the US I’m using the 2008 census data. All this is summarized in the table below, and my explanations follow.
| Age group | Number | Already immune | Infected | Vaccinated | Vaccinated uninfected | Number immune (low) | Number immune (high) | Percent immune (low) | Percent immune (high) |
| 0-18 years | 82,640,086 | 3,305,603 | 19,000,000 | 30,576,831 | 25,838,759 | 48,144,362 | 52,882,435 | 58.3% | 64% |
| 19-64 years | 182,549,922 | 10,952,995 | 33,000,000 | 38,335,483 | 32,570,355 | 76,523,350 | 82,288,479 | 41.9% | 45.1% |
| 65 and older | 38,869,716 | 13,215,703 | 5,000,000 | 11,334,214 | 6,751,594 | 24,967,298 | 29,549,918 | 64.2% | 76% |
| Totals | 304,059,724 | 27,474,302 | 57,000,000 | 80,246,530 | 65,160,708 | 149,635,010 | 164,720,833 | 49.2% | 54% |
1. Pre-existing immunity. A paper in New England Journal of Medicine last year2 found that 4% of children, 6% of young adults, and 34% of older adults (born before 1950; I’m going with 65 years old as the dividing line just to make it easier to compare to other data) were already immune to H1N1. That’s more or less consistent with other studies I’ve seen, so let’s go with that.
2. Infection. The CDC estimates that somewhere over 55 million people in the US were infected in the first and second wave of SOIV, and gives approximate age distribution here. I’ve used the mid-point of their range estimates, so it’s possible that significantly more people were infected. This works out to a quarter of US children being infected with SOIV, which is broadly consistent with measures elsewhere — for example, a recent Lancet paper3 that estimated that about a third of children in the UK were infected.
3. Vaccination. The CDC’s Anne Schuchat’s Feb 5 press conference was very useful for this. The CDC has estimated that somewhere over 70 million people in the US have been vaccinated. Schuchat gave two further figures: Some 37% of children, and about 21% of adults have been vaccinated. These figures come from two different sources — a CDC survey and a Harvard survey respectively — so they may not be directly comparable, and I don’t know the breakdown in adults (young adults vs. elderly) but these figures do work out to about the right total, around 80 million people. Probably a little high, but not by much.
Another source of fuzziness is how much overlap there is between infected people and vaccinated people. It’s probably safe to say that most vaccinated people were not subsequently infected, but it’s quite possible that people were infected (perhaps with no symptoms, which we know happened quite frequently) and were subsequently vaccinated. 4 I’ve tried to adjust for this by assuming that half of infected people didn’t know it, and went on to get vaccinated, 5 as well as subtracting the proportion of people who were already immune (who presumably had no way of knowing that). That’s the “Vaccinated uninfected” column. Or, I’ve assumed no overlap (just plain “Vaccinated”), to get an approximate range of immunity out there.
Including “Vaccinated uninfected” gives the “Number immune (low)”; assuming that all vaccinated were not infected gives the “Number immune (high)”.
And my conclusions are that:
- Over half the US population as a whole is now immune to the new SOIV.
- As many as three-quarters of the elderly and two-thirds of the children — the most important populations as far as flu is concerned — may be immune.
- Between a third and about half of this immunity was due to vaccination.
That level of immunity is probably enough to impact virus transmission drastically. In the early waves, if a child was infected then virtually every child she contacted in school or on the playground would be susceptible. Now only one in three of them are potentially infectable. I’ll have to spend some time looking at the models of influenza spread but I think that considering that the SOIV was not spectacularly infectious anyway, this level of population immunity is easily enough to prevent the third winter wave of disease I was expecting to see.
(I am particularly curious about modeling the impact of vaccination. Without vaccination would there have been a third wave? My guess is that there would have been, but that’s just a guess. Update for clarification: Vaccination rates were highest in children. Without vaccination only about 25% of children would be immune — vaccination therefore doubled or tripled the amount of immunity in this critical population, and I think SOIV would have resurged in schools in winter without this intervention.)
What’s more, this level of immunity, especially in the apparent absence of the usual seasonal flu strains, has important implications about influenza over the next few years, but this post is already too long, so maybe I’ll talk about that some other time.
- Probably quite accurate numbers are available, but not to me. Or, at least, not without a lot more work.[↩]
- Hancock, K., Veguilla, V., Lu, X., Zhong, W., Butler, E., Sun, H., Liu, F., Dong, L., DeVos, J., Gargiullo, P., Brammer, T., Cox, N., Tumpey, T., & Katz, J. (2009). Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus New England Journal of Medicine, 361 (20), 1945-1952 DOI: 10.1056/NEJMoa0906453[↩]
- Miller, E., Hoschler, K., Hardelid, P., Stanford, E., Andrews, N., & Zambon, M. (2010). Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study The Lancet DOI: 10.1016/S0140-6736(09)62126-7[↩]
- This is another significant potential source of error, I think.[↩]
- That is, I’ve subtracted that proportion of people from the vaccinated totals.[↩]
Professor York
Professor R on Virology reviewed research on the efficacy of various vaccines on novel 2009 H1N1, that were derived from 1918, 1976, and other H1N1 strains, tested in vivo in mice. Most of the vaccines effectively cross-reacted with 2009 H1N1. Also there wasnt much antigenic drift in H1N1 in swine. One striking implication is that the much-maligned 1976 swine flu vaccination effort, which had an uptake of around 40 million Americans, may have a conferred a mitigating or protective effect on the population, and in particular for persons aged over 35. If this is the case, I wonder how that might factor into your calculations on population immunity ?
Best Regards
Ed (Editor) Influenza Monitor
http://influenzamonitor.com
http://twitter.com/influenzamon
This is the first time I see all the relevant data pulled together, and even if numbers may vary your conclusions seem robust. I’m just wondering why you didn’t use the CDC estimates of h1n1 cases. Not really an issue, I made your calculations and your conclusions still hold.
I find a bit puzzling your assessment of SOIV as “not spectacularly infectious anyway”. Although (according to surveillance data) the rate of increase of the epidemics was high but not spectacular, it ended up infecting a significant portion of the population, especially children. Some more maths would be needed here, but it seems that infectiousness was greater than what was shown by the weekly epidemiological reports. This would slightly increase the residual chances of a third wave.
One last question: have you got any reference to share about epidemiological models specifically addressed to a second or third wave, i.e. when a significant part of the population is not susceptible? In Italy we had only one short, acute epidemic wave, an estimated number of cases less than 8% of the population, and very low levels of vaccination. Unless most cases went undetected, the arrival of a second wave here cannot be ruled out.
I’m just wondering why you didn’t use the CDC estimates of h1n1 cases. Not really an issue, I made your calculations and your conclusions still hold.
I could try to give a complicated explanation, but I just couldn’t find them! Thanks for pointing it out. My guesstimates look to have been on the high end for children, on the low end for young adults and the elderly, but the overall conclusions aren’t much changed by using the CDC estimates.
I find a bit puzzling your assessment of SOIV as “not spectacularly infectious anyway”.
I was basing that on a number of studies, such as the recent CMAJ paper, that found a relatively low R(0) for the SOIV.
CMAJ. 2010 Feb 9;182(2):131-6.
Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza.
Tuite AR, Greer AL, Whelan M, Winter AL, Lee B, Yan P, Wu J, Moghadas S, Buckeridge D, Pourbohloul B, Fisman DN.
One last question: have you got any reference to share about epidemiological models specifically addressed to a second or third wave, i.e. when a significant part of the population is not susceptible?
I haven’t spend enough time looking over the epidemiological models. In spite of a relatively homogeneous virus worldwide, a number of countries seem to have been outliers in terms of percent of population infected for no obvious reason (or at least for not reason that’s obvious to me; I’m no epidemiologist).
One striking implication is that the much-maligned 1976 swine flu vaccination effort, which had an uptake of around 40 million Americans, may have a conferred a mitigating or protective effect on the population, and in particular for persons aged over 35. If this is the case, I wonder how that might factor into your calculations on population immunity ?
The short answer is that this effect didn’t show up in the study looking at pre-exposure immunity to SOIV. I don’t know enough about the 1976 vaccination; I suspect that there would have been geographical concentrations of vaccination that might not have shown up in the relatively small study.
But let’s take a quick and superficial look at the numbers. People over 26 years old vaccinated in 1976 would now be in the cohort (born pre-1950) that was shown to have a significant level of immunity to modern SOIV.
What about those under 26 in 1976? That’s very roughly a third of the population. If the 1976 vaccination was spread evenly over the population by age that would be about a third of 40 million or about 13 million people (I suspect the vaccination was not homogeneous by age or geography but let’s set that aside). Those 13 million people would now fall into the modern cohort of Americans between 19 and 64 years old, about 180 million people, and would comprise about 7% of them. That cohort was found to have roughly a 6% level of pre-existing immunity to SOIV. Considering falling titers and so on, conceivably the 1976 vaccinees could account for the difference in pre-existing immunity between this cohort and the younger group (the under-18s).
Yes, there’s a ton of hand-waving there, but I think it does indicate that we shouldn’t expect a massive impact from the 1976 vaccination.
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Professor York
Thanks very much for taking the time to walk through this. Back of the envelope, it appears that the percentage of persons in the 19-64 age cohort that could have been vaccinated in 1976 (7%) fits almost perfectly the estimate of pre-existing immunity for that cohort from the NEJM study (6%).
This would be harder to sort out. I also wonder what impact the 1976 vaccinations may have had in the pre-existing immunity of seniors to SOIV. Perhaps the 1976 vax effort may have been relatively more helpful to them. The serological study in Lancet as I recall suggested potential lower/upper bounds of 25%/67% pre-existing immunity for seniors, depending on the technique employed.
Thanks Again,
Ed
Back of the envelope, it appears that the percentage of persons in the 19-64 age cohort that could have been vaccinated in 1976 (7%) fits almost perfectly the estimate of pre-existing immunity for that cohort from the NEJM study (6%).
Although it’s worth noting that even children in that study had around a 4% rate of pre-existing immunity. Who knows where that came from, but if it also affected the somewhat older cohort then there’s only an extra 2% that could be the 1976 vaccine effect.
The larger point (without getting bogged down in numbers that are not very precise to start with), I think, is that the 40 million vaccinees wouldn’t have as large an impact on pre-existing immunity as you’d think at first glance, even without taking into account the gradual loss of immunity over 33 years.
[...] How many Americans are immune to H1N1? [...]
Dr York
As you say, we should not overstate the impact of the 1976 vaccine.
Just one last back of envelope calculaton… or… one last speculation really.
If around half of the remaining persons who were vaccinated in 1976 (persons age 27 and higher) survived to older age, (say another 13 million ?) could that possibly account for much of present-day pre-existing immunity among present day seniors, who number around 39 million ?
Thanks again,
Ed
If around half of the remaining persons who were vaccinated in 1976 (persons age 27 and higher) survived to older age, (say another 13 million ?) could that possibly account for much of present-day pre-existing immunity among present day seniors, who number around 39 million ?
It makes sense, but it doesn’t fit into the observations worldwide that older people in general have immunity to the new SOIV. Since the swine flu vaccine wasn’t given outside North America (as far as I know, and I’m not positive about Canada even), it can’t account for the widespread immunity in older people in the UK and other places.
I think there’s just too many unknowns and not enough large studies to make strong a cases about the present impact of the 1976 vaccination, although it’s likely that there is at least some remaining impact.
[...] of pre-existing immunity) gets a little complicated. An exchange with Professor York, who pens Mystery Rays from Outer Space, (MRFOS) suggests some protective effect from the 1976 vaccines exists, but that it should not be [...]
PLOS Currents paper:
Seroprevalence Following the Second Wave of Pandemic 2009 H1N1 Influenza. Ross, Zimmer, Burke, Crevar, Carter and Stark.
http://knol.google.com/k/seroprevalence-following-the-second-wave-of-pandemic-2009-h1n1-influenza?
I saw a recent Lancet paper that suggested an infection rate of 1 in 3 for children.
http://press.thelancet.com/h1n1inengland.pdf.
Didn’t the CDC report ~20% vaccination rate in the US population?
If we sum an estimated 60 million vaccinated and another 65 million who contracted the virus, with another 15-20% having some cross-protection from either pandemic or seasonal H1N1, the potentially protected CDC guesstimate of approximately half the US population sounds reasonable.
A possible explanation for the lack of a severe second wave in the US and Canada?
Blame the diminished global economy, at least in part. Slowdown in air travel, more people staying at home.
There has been a minor uptick in activity across North America and Europe in the past month: that’s the weather.
The lack of a expected heavy wave in the Southern Hemisphere was due to different factors at play.
Protracted wave propagation in Asia can also be blamed on the economy (flipside reasoning) and far-from-normal weather.
You do realize that had contributing factors not diminished this past Fall, the 2010 Winter Olympics in Vancourver might have been a disaster, coming in midst of what should have been a strong second wave of infection?
We are not out of the woods yet. The fickle and foolish general population may have thought the pandemic response by CDC and WHO to be overblown, but they haven’t a clue just how close we came to a real hummer infectious event: a minor gap between thumb and forefinger.
That close.
Very interesting: very low seasonal influenza rate. Higher in Asia. Hmmmm.
[...] On the flu front, York `did the math’ and came up with a reasonable approximation on the level of herd immunity we likely have in the United States to novel H1N1 in How many Americans are immune to H1N1? [...]
With the advent of the world cup (soccer) arriving soon to south Africa – we are constantly getting press coverage as to how the virus is going to spread at a very fast rate during this tournament. You see it combines with our “flu” season at the same time.
the real question is – is this just people selling newspapers or is there a real threat to our country and any of its visitors during the world cup?
we are told that our health system is prepared and able to cope – but this is still Africa, and a lot of loosely said statements cover problems.
I guess only time will tell.
Rob
Why are American Indians and Alaskan Natives at increased risk of dying due to h1n1.
Thanks. There is no doubt that a strong immune system is important.