Shots in the Dark?

More elderly are getting their recommended flu shots, yet flu-related deaths continue to rise. A new study suggests that the vaccine's effectiveness is overestimated and could prompt investigation into better ways to protect older people against influenza.

Since the 1960s, the government has recommended that people aged 65 or older get vaccinated against the flu--sensible advice, considering that past studies have attributed a 50% decrease in death in the elderly to the flu vaccine.

But after crunching 3 decades' worth of data, epidemiologist Lone Simonsen of the National Institute of Allergy and Infectious Diseases says that these estimates are overblown. Although she and her colleagues do not recommend that seniors skip their vaccines, they hope that their findings will spur exploration of other means for preventing the estimated 36,000 flu-related deaths in the United States each year.

Simonsen was inspired to reexamine the data on vaccination benefits by a perplexing paradox: Although the number of seniors receiving flu shots has increased dramatically over the years--from 15% to 20% in the 1970s to 65% in 2001--the number of flu-related deaths has also grown.

At first, Simonsen chalked up the discrepancy to an aging population and nastier viruses. Because the elderly are more likely to die from flu-related illnesses than their younger counterparts are, Simonsen reasoned, the number of flu-related deaths might rise along with the proportion of elderly in the population. In addition, more virulent strains of influenza have appeared with greater frequency over the past 10 years.

So she and her colleagues reanalyzed the data, controlling for the increase in the average age of the U.S. population and separately handling data for the most virulent viruses. They found that the number of flu-related deaths over the past 20 to 25 years has remained fairly constant--not what one would expect if the vaccine were working as well as past studies claim.

Assessing directly how the vaccine affects mortality is challenging, because pinpointing exactly how many deaths are attributable to influenza is difficult: Infection is not often confirmed by lab tests or noted as a cause of death on death certificates. To sidestep this problem and cast the broadest net for collecting flu-related deaths in the elderly, Simonsen and her colleagues used a mathematical model that allowed them to tease out the seasonal spike in mortality that coincides with influenza virus circulation.

"The paper is intriguing and important," says epidemiologist Trang Vu of the Health Economics Unit at Monash University in Australia, who participated in a large meta-analysis of vaccine effectiveness. She agrees with Simonsen's conclusion that further investigation is needed to sort out the disparity between the rise in vaccination coverage and nondeclining mortality rates. Vu notes, however, that Simonsen's study includes data from all flu seasons, regardless of whether the vaccine being distributed matched the predominant flu strain in circulation; thus, her study examined the effectiveness of the overall vaccination program, not necessarily the vaccine itself.

Officials at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, continue to support the current recommendation that people aged 65 or older get a flu shot each year and do not intend to revise the policy based on the new data, which was published in the February 2005 issue of Archives of Internal Medicine. "Lone's paper represents one study that shows potentially that the vaccine isn't working, but we have many other studies showing that the vaccine is effective in reducing influenza-related hospitalizations and deaths," says CDC epidemiologist William Thompson. "I don't think one study should outweigh the others."

Simonsen also encourages seniors to get vaccinated. The flu shot does prevent some deaths, she found in her study--just not as many as previously estimated. Furthermore, the vaccine could have significant health benefits. "We only looked at mortality," says Simonsen. "There are possibly more morbidity benefits." In future investigations, such information could be gleaned by examining data from hospital health records, she notes.

As for the current study, Simonsen says that the findings should prompt further investigation into how to protect the elderly from influenza. Some researchers are working on making vaccines that are more senior-friendly. The elderly often do not produce as hearty an immune response as younger folks do (see "For the Elderly, Vaccines Often Miss Their Mark"). In particular, seniors' immune systems can have trouble producing the cells they need to remember past infections. "Trying to generate immunological memory in older people just doesn't work very well," says immunologist Laura Haynes of the Trudeau Institute in Saranac Lake, New York. Studying the physiological changes that occur as the immune system ages might lead to the development of vaccines that prevent infection in seniors whose immunity is on the wane.

Other researchers are trying to outline prevention strategies that go beyond vaccinating the elderly. One approach is to vaccinate everyone else. For example, in the February 2005 issue of the American Journal of Epidemiology, biostatistician Ira Longini Jr. of Emory University's Rollins School of Public Health in Atlanta, Georgia, proposes concentrating on vaccinating schoolchildren, the age group most responsible for the spread of influenza. "The best way to protect people who wouldn't respond well to a vaccine is to protect them from being infected or reduce risk of infection and reduce transmission in the whole population," he says.

In addition, health care workers and caretakers should make an effort to avoid exposing the elderly to infected individuals, particularly in hospitals and nursing homes, says Jonathan McCullers, an influenza researcher in the Department of Infectious Diseases at St. Jude Children's Research Hospital in Memphis, Tennessee.

Experts also advocate more aggressive use of antiviral medications to control the spread of flu. These drugs reduce viral propagation without relying on the body's own defense mechanisms, making them promising therapies for individuals who don't respond well to vaccines, note Longini and McCullers. At the onset of a flu outbreak, such medications can be administered to the sick or even as a preventive measure to individuals in close contact with the elderly.

Until such measures become commonplace, however, older folks should continue lining up for their traditional flu shots each fall--but preferably not near the local elementary school.

Nicole Garbarini is a freelance writer based in Nashville, Tennessee, who didn't cut in front of any senior citizens to get a flu shot this season.