Researchers estimate relatively low H1N1 fatality rate

Dec 8, 2009 (CIDRAP News) – Researchers who analyzed H1N1 influenza hospitalization and death data from the early months of the pandemic say the fall-winter phase of the contagion may bring fewer deaths than an average flu season, barring any changes that would make the virus more virulent, but the deaths are likely to be in younger age-groups.

Using data from Milwaukee and New York City, an American-British team used two different approaches to estimate case-fatality rates (CFRs) among symptomatic patients. One approach yielded a CFR of .048, or roughly 1 death per 2,000 patients, while the other approach yielded a CFR about 9 times lower than that.

However, the study also indicated that death rates were highest in adults between 18 and 64 years old and children up through age 4, unlike the pattern with seasonal flu, which mostly kills elderly people. The study was published last night in the online journal PLoS Medicine.

"These estimates suggest that an autumn-winter pandemic wave of H1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64," states the report.

The authors, however, caution that their estimates are based on a number of assumptions and that various factors, such as an increase in viral virulence or drug resistance, could change outcomes in the coming months.

Dr. Marc Lipsitch of the Harvard University School of Public Health, senior author of the study, said in a press release that it is still important to vaccinate people against the virus and to stay vigilant about disease in groups at risk for complications,

"This is a serious disease," he said, noting that high-risk groups such as pregnant women, people with asthma, and those who have weakened immune systems should be vaccinated and should seek treatment promptly if they have suspicious symptoms.

Two estimation methods
The authors used data from early April to mid July. The Milwaukee data included medically attended H1N1 cases and hospitalizations, while the New York data consisted of hospitalizations, intensive care unit (ICU) and ventilator use, and deaths. In addition, the researchers used the results of telephone surveys in May and June of self-reported flu-like illness among New Yorkers.

In one estimation approach, the authors used survey findings from the Centers for Disease Control and Prevention (CDC) on the proportion of people with flu-like illness who seek medical attention and combined it with the Milwaukee data on H1N1 cases and hospitalizations and the New York data on hospitalizations, ICU cases, and deaths.

This first approach yielded the CFR estimate of .048%, with a credible interval (CI, or range in which the true value is likely to be) of .026 to .096. Further, this method yielded estimates that .239% of patients, or about 1 in 400, required intensive care and that 1.44% were hospitalized.

In their second approach, the researchers used the New York telephone survey results (in which about 12% of respondents reported flu-like symptoms) to estimate the number of symptomatic cases in the population and combined it with the New York data on hospital cases, intensive care use, and mortality.

This method yielded 7- to 9-fold lower estimates than the first method: a CFR of .007 (CI, .005% to .009%), an intensive care rate of .028% (CI, .022% to .035%), and a hospitalization rate of .16% (CI, .12% to .26%).

A recent CDC estimate of the pandemic fatality rate lies between the two estimates from the authors. Dr. Martin Cetron of the CDC, during a Nov 30 webcast on lessons of the 1918 pandemic, estimated the CFR at .018%. His estimate apparently was based on a CDC report released Nov 12, in which the agency estimated that the nation has had 22 million H1N1 cases and 3,900 deaths.

Fatality rates highest in adults
Both approaches used by the PLoS Medicine authors indicated the CFR was highest in adults and lowest in school children (ages 5 to 17), the report notes. The first approach showed the CFR was highest in 18- to 64-year-olds (.090%) and somewhat lower in those over 65; the second showed about the same rate in both of those groups, but data on the elderly were sparse.

The authors list several sources of uncertainty that could affect their estimates. Given the number of uncertainties, "we believe that our two approaches probably bracket the reasonable range of severity for the US spring wave" of H1N1, they write.

They also note that their estimates reflect the availability of antiviral drugs and other treatments that will not be available in all populations. Although the health systems in both Milwaukee and New York were strained during the period studied, there was no shortage of intensive care or other life-saving resources, they state. They suggest that the death rate could be four to five times higher in a population lacking access to intensive care.

Comparing their estimates with evidence on seasonal flu, the authors say their first approach suggests that US pandemic deaths could range anywhere from about half as many to nearly twice as many as in an average flu season, whereas the second approach suggests the toll could be 10-fold lower than in an average season.

Overall, they state, "The estimated severity indicates that a reasonable expectation for the autumn-winter pandemic wave in the US is a death toll less than or equal to that which is typical for seasonal influenza, though possibly with considerably more deaths in younger persons." They note that either set of estimates puts the pandemic in the lowest severity category (category 1, with a CFR up to 0.1%) considered in pandemic planning before the virus emerged.

However, they also caution, "A change in the virus to become more virulent or resistant to existing antiviral drugs , or the emergence of more frequent bacterial coinfections, could increase the severity of infection compared to that observed so far."

Praise and caveats
Lone Simonsen, PhD, MS, a professor and research director in George Washington University's Department of Global Health, said the study "uses a clever statistical approach to get closer to the true case-fatality ratio." Simonsen noted that she served as PLoS Medicine's academic editor for the paper, meaning she helped find reviewers for it, but was not involved in the study.

"The estimated case-fatality ratio is in good agreement with similar estimates from New Zealand. But notice that the confidence interval is still pretty wide, a 10-fold range," she told CIDRAP News.

But she added some caveats: "The data used in this study were from the summer wave, so if anything changes for the worse, for example increased circulation of pathogens that may worsen the outcomes, or if colder weather matters, then the estimates will be in the low end when the authors seek to extrapolate from the case-fatality ratio to a total 2009-2010 pandemic burden estimate."

Simonsen noted that fatality rates can change in successive waves of a pandemic, as occurred in the 1918-19 event. "I think we shall have to wait until spring 2010 at the earliest to evaluate the total burden of 2009 H1N1 influenza," she said.

In addition, it's difficult to compare the mortality impacts of the current pandemic and seasonal epidemics, because the age range most affected by the pandemic is 30 to 50, whereas the average age of those who die of seasonal flu is around 75, Simonsen commented.

Presanis AM, De Angelis, D, New York City Swine Flu Investigation Team, et al. The severity of pandemic H1N1 influenza in the United States, form April to July 2009: a Bayesian analysis. PLoS Med 2009 Dec;6(12) [Full text]

See also:

Dec 7 Harvard School of Public Health press release
http://www.hsph.harvard.edu/news/press-releases/2009-releases/severity-h1n1-flu-us-current-flu-season-may-be-less-than-fea.html

Nov 12 CIDRAP News story "CDC's new estimation method raises H1N1 numbers"

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