How many people die from influenza?

16 June 2009

WHO reports that as of 15 June 2009, 76 countries have officially reported 35, 928 cases of influenza A(H1N1) infection, including 163 deaths. These numbers can be used to calculate a case fatality ratio (CFR) of 0.45%. Is this number an accurate indication of the lethality of influenza?

Determining how many people die from influenza is a tricky business. The main problem is that not every influenza virus infection is confirmed by laboratory testing. For example, early in the Mexico H1N1 outbreak, the apparent CFR was much higher because the total number of infections had not been established. Even with the intense surveillance being conducted at the onset of this pandemic, many infections are still not diagnosed. Virologic surveillance is likely become even more incomplete as health systems become overburdened:

The size of Victoria’s outbreak is now so great that only those most at risk – the elderly, pregnant women and those with other underlying medical conditions – are being tested, resulting in 199 new cases last week. “At the moment cases confirmed in the laboratory signify only a small fraction of the cases,” Dr Lester said. “It could be three or four times the laboratory confirmed number, but it’s very hard to estimate, given the mild nature of the virus. It is not anywhere near the one in three some have suggested.

So how do we determine how many people are killed by influenza virus?

In fact, the Centers for Disease Control and Prevention of the US does not know exactly how many people die from flu each year. The number has to be estimated using statistical procedures.

There are several reasons why influenza mortality in the US is estimated. States are not required to report to the CDC individual influenza cases, or deaths of people older than the age of 18. Influenza is rarely listed as a cause of death on death certificates, even when people die from influenza-related complications. Many flu-related deaths occur one or two weeks after the initial infection, when influenza can no longer be detected from respiratory samples. Most people who die from influenza-related complications are not given diagnostic tests to detect influenza.

To determine the level of influenza-related mortality, each week, from October to mid-May, the vital statistics offices of 122 cities report the number of death certificates which list pneumonia or influenza as the underlying or cause of death. The percentage of deaths due to pneumonia and influenza are compared with a seasonal baseline and epidemic threshold value determined each week. The seasonal baseline is calculated using statistical procedures using data from the previous five years, and the epidemic threshold is calculated as 1.645 standard deviations above the seasonal baseline. This is the point at which the observed proportion of deaths attributed to pneumonia or influenza becomes significantly higher than would be expected without substantial influenza-related mortality.

For the 2007–08 influenza season, the percentage of deaths attributed to pneumonia and influenza exceeded the epidemic threshold for 8 consecutive weeks from January 12–May 17, 2008, with a peak at 9.1% at week 11, as shown below. In contrast, pneumonia and influenza deaths remained below the epidemic threshold in the relatively mild 2008-2009 season:

2009-influenza-mortality

This method clearly is not perfect. The rationale is that the ‘excess mortality’ (over the epidemic theshold) is likely to be caused by influenza, but so could at least some of the deaths between the baseline and excess threshold. For example, the pneumonia and influenza deaths are below the epidemic threshold this season, yet we know that people have died from influenza. It also misses deaths caused by influenza, but for one reason or another influenza or pneumonia were not entered on the death certificate.

The answer to this dilemma is more statistics – methods that use the CDC data to estimate the number of deaths caused by influenza. In the paper cited below, the authors calculated an average of 41,400 deaths each year , for the years 1979 – 2001, in the US due to influenza. Remember that this is an average, and the actual numbers may vary substantially each year.

To answer the question posed at the beginning of this post: except in well-contained outbreaks in which the number of infected individuals can be determined with precision, the case-fatality ratio is bound to be inaccurate. The use of serological assays to determine the extent of infection, coupled with statistical estimates of influenza mortality, are likely to provide more reliable data.

Dushoff, J. (2005). Mortality due to Influenza in the United States–An Annualized Regression Approach Using Multiple-Cause Mortality Data American Journal of Epidemiology, 163 (2), 181-187 DOI: 10.1093/aje/kwj024

  • http://www.virology.ca/ Chris Upton

    Excellent info!
    I think there's a lot of different types of good data collected on disease/death incidence but often it get reused in inappropriate ways.
    The one that bugs me the most is calculating a case fatality rate on simple numbers of confirmed cases, when these are reported to be much lower than actual case number.
    Thanks for the blog.

  • http://www.klxmedia.com Christian Sinclair

    Thanks for the great post. As a hospice physician who signs many death certificates, I had never once written influenza, so I always wondered how they got these numbers. Nor had I noticed it on discharge summaries or hospital progress notes. The true mortality rate is really unknown in this case.

    Here is a post about the 1918 Influenza epidemic from a 3rd year medical student that was published a few years ago in Annals of Internal Medicine. http://arts.pallimed.org/2009/02/influenza-in-1

    (PS Found you via Research Blogging. Glad to see you using it, I do too at Pallimed)

  • http://www.setbb.com/fluwiki2/viewforum.php?f=7&sid=c1408b5cf8a576350c571da5192e08b5&mforum=fluwiki2 gsgs

    published each week in MMWR (last page)
    http://www.cdc.gov/mmwr/PDF/wk/mm5822.pdf
    old weeks available

    weekly deaths from pneumonia and influenza in New York City
    weeks 17,2008 – 22,2009:

    55,57,43,46,52,39,48,31,41,32,26,46,41,41,32,43,44,31,45,32,36,33,27,31,30,31,32,40,43,39,37,38,52,
    42,25,??,51,63,52,60,52,54,53,47,55,43,46,49,45,61,45,33,34,32,44,23,51,30,42

    average:42.5 per week

    weeks 17-22,2009: 222 (37 per week)
    weeks 17-22,2008: 292 (48.7 per week)

    70 fewer deaths this year than in the same period last year.

    ~250 excess deaths from seasonality in NYC in 2008/9

    15 weeks with most deaths : 53/2008-14/2009 = 776 (51.7 per week)
    15 weeks with fewest deaths: 29/2008-43/2008 = 529 (35.3 per week)

    no effect from Mexflu visible

  • Rob

    Thank you for the post. I had one question:

    CFR ratio =0.45% significant/insignificant?

    In other words, how do I interpret CFR ratio? Is there any baseline below which its normal else significant?

  • http://www.virology.ca/ Chris Upton

    Tricky.
    If it was really 1 in 200 dying, it would be total disaster.
    One way to look at CFR might be to count deaths per hospitalization; not perfect either.
    But it focuses on serious cases and outcome, rather than just whether we're testing for infection.
    Numbers of hospitalizations is probably a better number than “confirmed cases”, as well.
    At least it means a bit more to me.

  • http://www.virology.ws profvrr

    I would say that any CFR based on laboratory confirmed cases is about
    a ten-fold overestimate. There are probably at least ten times more
    cases of influenza infection than those confirmed by laboratory tests.
    See Chris Upton's comments here as well.

  • gonzo's wife

    The question is… how do they determine the case fatality rate for typical seasons? Do they use mathematical modeling based on confirmed cases in surveillance? Do they use confirmed cases only? If there are truly over a million cases of H1N1 in the US, the CFR for the disease is .0001 or less. Way less than “seasonal influenza”. The hospitalization rate at near 15 % would be less than .3%, again, way less than seasonal flu. Without the ability to compare how the CFR is being determined between the H1N1 or the seasonal flu, how will we know whether next season will be concerning or not? and if Argentina usually has 2000 or more deaths a year from influenza, why are they concerned over 50 during their typical flu season?

  • HansBonaire

    That sounds very plausible, but according to that same reasoning, isn't it possible that the same thing goes for the number of deaths? I mean that there are/could be 10 times more deaths because a lot of people don't even get tested or are being recognized as flu patients?

  • Pingback: Some clarity on case fatality ratios | Swine Flu Daily Update()

  • http://www.virology.ws profvrr

    CFR for seasonal flu is calculated by determining excess P&I mortality
    as described in the post. The number of infections is modeled based on
    lab confirmed cases. I don't know why Argentina is concerned; they
    should not be.

  • http://www.virology.ws profvrr

    Yes, the deaths reported as flu are variable, as discussed in the
    post. That's why they are calculated statistically as a multiple of
    P&I related deaths.

  • Pingback: This Week In Virology – Esta Semana en Virología « Gripe por A (H1N1) Blog()

  • chauna sims

    This is good information

  • chauna sims

    This is good information

  • Pingback: How Serious is H1N1? Deaths and Transmission Rate Uncovered :: hippie dippie bébé()

  • Jilesb11

    my grandson die from  this he was jest 18 month the dortor didnot unit he die

  • Shirley Hamilton

    Great information here. It is real sad the amount of lives lost each year to this sickness. I know I do not hesitate to talk to a doctor. That way I know I am getting the best health care.

  • Pingback: H7N9 Virus and You. - Unite The Gods()

  • Pingback: Banoosh » » H7N9, Viruses and You()

  • http://www.abicana.com/shop2.htm Knut Holt

    How many die or get serious complication from flu vaccine. Never spoken about, but complications are frequent and sometimes serious.

    The low effectiveness weighted up afainst frequent side effects, seriously cast the current vaccine recommendations in doubt.
    Regards Knut Holt

    http://www.panteraconsulting.com