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:
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