Effect Measure

It was some time after the pandemics of 1957 and 1968 that we were able to judge their severity and it will likely be some time after this one has finally burned itself out, most likely to become “just another” seasonal flu, that we will be able to gauge the 2009 swine flu pandemic. A lot of data is being generated but it will take time to harvest it and send it to the scientific market for consumption. A report in today’s Lancet reminds us that we aren’t seeing all there is to see, even with unprecedentedly rapid means of communication and better surveillance than ever in the history of our long battle with the influenza virus:

Around one child in every three was infected with 2009 pandemic H1N1 in the first wave of infection in regions with a high incidence, ten times more than estimated from clinical surveillance. Pre-existing antibody in older age groups protects against infection. Children have an important role in transmission of influenza and would be a key target group for vaccination both for their protection and for the protection of others through herd immunity. (Miller et al., “Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study,” The Lancet, Early Online Publication, 21 January 2010doi:10.1016/S0140-6736(09)62126-7)

This study used blood samples drawn in 2008 (before the pandemic struck) to measure the prevalence of antibody in various age groups thought to sufficient to protect against the swine flu virus that emerged in 2009. We don’t know the source of the low level of reacting antibody seen in a percent or two of children at that time (it is likely from cross reaction with another flu virus) but it is pretty clear that the circulating pandemic virus caused the ten fold increase seen in children after the first wave struck around London the spring and summer of the following year. Not all areas of England were equally affected nor were all ages. Increases in antibody prevalence in young adults and older age groups were much less and negligible in the oldest group:

In the study, the authors obtained 1,403 serum samples taken in 2008 (baseline-before the first wave of H1N1 infection) and 1,954 serum samples taken in August and September, 2009 (after the first wave of infection) as part of the annual collection for the HPA?s seroepidemiology programme from patients accessing health care in England.

They then calculated the proportion of samples that had a level of pandemic H1N1 antibodies high enough to confer immunity in each age group, at baseline and in August and September 2009.

In the baseline samples, the proportion of people with immunity varied from 1.8% in the 0-4 year age group to 31.3% in those aged over 80 years.

The proportions of August and September 2009 samples with immunity showed a significant age and geographical variation. The highest increases were in London and the West Midlands, where infection rates were highest.

For 0-4 year olds, the immunity rate increased from 1.8% at baseline to 21.3% in September 2009; for 5-14 year olds, the increase was from 3.7% to 42%, and for 15-24 year olds, the increase was from 17.5% to 20.6%. (Onmedica)

These data confirm what models predicted and everyone suspected: there was much more infection with this virus than suggested by only counting clinical cases. Seasonal flu infections are clinically often very mild or even asymptomatic. That’s good news for most people but the bad news is that when millions of people are infected it doesn’t take a very high rate of more severe outcomes to fill up hospitals or empty schools and workplaces. Exactly why some people fare worse (or better) than others is not understood. We know there are some risk factors that increase your chances of a bad outcome, just as with severe auto accidents speed and alcohol are risk factors. Unfortunately they are not the sole predictors and thousands of people are killed or crippled on the road every year even though they weren’t driving too fast or under the influence. Similarly, influenza, especially pandemic strains, can kill otherwise healthy people of any age, and this year has seen many such tragic cases.

These data also confirm the value of routine surveillance. The blood sera used for baseline were part a routine surveillance program of the UK’s Health Protection Agency used for evaluating the immune status of the population for diseases like measles, mumps and rubella. They are not a perfect representation of the population, having been obtained from what’s left over from clinical laboratory samples done for other purposes. A population based sample would have been better and perhaps after this pandemic we will see various national health agencies instituting routine seroprevalence data collection.

Meanwhile the second guessing about over reaction to this pandemic continues. In our view it is irresponsible, but whether you agree about that harsh judgment or not, it is quite clear it is premature. We won’t know the full measure of this pandemic for a few years.

We may have many new tools to peer into this ongoing pandemic, but the flu virus is still able to keep secrets.

Comments

  1. #1 Jupe
    January 22, 2010

    “for 5-14 year olds, the increase was from 3.7% to 42%”

    That infection rate is amazing, and I wonder if that’s part of how pandemic strains mysteriously “eradicate” the former seasonal strains? Such a high prevalence would allow for direct competition between seasonal and pandemic strains.

  2. #2 anon
    January 22, 2010

    > Around one child in every three was infected with 2009 pandemic H1N1 in the first wave
    > of infection in regions with a high incidence, ten times more than estimated from clinical
    > surveillance

    so, they had estimated that only 3.3% had been infected ? Who had estimate that ? Source, please.

    > [baseline immunity] is likely from cross reaction
    > with another flu virus

    exposure to American swine.
    Or some usually rare epitopes (randomly) happened
    to cause much immuntity production

    > Exactly why some people fare worse (or better) than others is not understood.

    understand it and flu is no longer a problem. Should be easy.
    Let’s all get it asymptomatically.

  3. #3 Vicki
    January 22, 2010

    Anon–Understanding does not mean controlling or curing, useful as it may be for that. It could turn out that why some people fare better is largely genetic. There might be co-morbidity issues, which leaves the problem of figuring out how to control one or more other infections. (I’m guessing that if it was a straightforward environmental issue, we’d know about it by now: if smokers and those who lived with them did a lot worse, someone would have noticed.)

  4. #4 Jupe
    January 22, 2010

    With unusually mild cases, it might have to do with a small viral load you’re exposed to, or an accidental cross-reactive immunity to something else.

    With unusually severe cases, I’ve always suspected it’s a matter of really bad luck a lot of times, involving co-infection with some other germ(s?), like parapertussis or RSV or something.

  5. #5 tetano
    January 23, 2010

    122 cities P&I mortality still remains high despite low levels of pandemic virus, the absence to date of the seasonal virus and despite pneumonia and influenza mortality for the elderly remains at low levels.
    In the following site, I published a table of mortality for P&I which shows that in the last weeks of 2009( 40-52) the number of deaths was higher for PI than the previous 6 years and the mortality of elderly was lower. The only age group where the level of mortality appears to be high is 45-64

    http://www.swineflu.org/forum_posts.asp?TID=31909