The influenza vaccine, which has been strongly recommended for people over
65 for more than four decades, is losing its reputation as an effective way to ward off the virus in the elderly. A growing number of immunologists and epidemiologists say the vaccine probably does
not work very well for people over 70, the group that accounts for three-fourths of all flu deaths. The latest blow was a study in The Lancet last month that called into question much
of the statistical evidence for the vaccine's effectiveness.
The authors said previous studies had measured the wrong
thing: not any actual protection against the flu virus but a fundamental difference between the kinds of people who get vaccines
and those who do not. This contention is far from universally
accepted. And even skeptics say that until more effective measures are found, older people should continue to be vaccinated,
because some protection against the flu is better than none.
Still, the Lancet article has reignited a longstanding
debate over claims that the vaccine prevents thousands of hospitalizations and deaths in older people. "The whole notion of
who needs the vaccine and why is changing before our eyes," said Peter Doshi, a doctoral candidate at M.I.T. who published
a paper on the historical impact of influenza in May in The American Journal of Public Health. The Lancet paper, by Michael L. Jackson and colleagues at the Group Health
Center for Health Studies in Seattle, was based on an analysis of medical charts of thousands of elderly members of an H.M.O.
The study found that people who were healthy and conscientious about staying well were the most likely to
get an annual flu shot. Those who are frail may have trouble bathing or dressing on their own and are less likely to get to
their doctor's office or a clinic to receive the vaccine. They are also more likely to be closer to death.
Dr. David K. Shay of the Centers for Disease Control and
Prevention, a co-author of a commentary that accompanied Dr. Jackson's study, agreed that these measures of health and frailty
"were not incorporated into early estimations of the vaccine's effectiveness" and could well have skewed the findings.
Not everyone is sold on the significance of the Lancet
study. "I think this is another study that provides interesting findings and raises questions," said Dr. Kristin Nichol, chief
of medicine at the Veterans Affairs hospital in Minneapolis. "I don't think we know yet what the final word is on influenza
vaccinations in the elderly. “ "I really feel, and I feel very strongly about this, that the
public health message should be that vaccines are effective," she continued. "I don't think that science is necessarily best
hashed out in the media."
Dozens of studies since 1960 have supported the view that
the vaccine is a powerful protector of the elderly, cutting their risk of dying in winter from any cause by almost 50 percent
and reducing the risk of hospitalization by nearly 30 percent. Those
findings came from observational studies, in which scientists make inferences about the effect of a treatment on a population
by comparing what happens to a group that has the treatment with what happens to an apparently similar group that does not.
There has been only one large study that compared
the flu vaccine with a placebo for two random groups of older people in which neither the patients nor the scientists knew
which group was receiving which injection. It came to a different conclusion from the observational studies. Conducted by
Dutch researchers and published in 1994 in The Journal of the American Medical Association, it found that in those 60 to 69,
the vaccine prevented influenza about 57 percent of the time. In those over 70, the vaccine prevented the flu just 23 percent
of the time, though the estimate is imprecise because the study was not designed to look at this age group.
Because of this failure to rely upon the placebo-controlled
trials, which are considered the gold standard in medical evidence, health policy was based flawed studies. "I think the evidence base we have leaned on is not valid," said Lone Simonsen, an epidemiologist and visiting
professor at the George Washington University School of Public Health and Health Services in Washington who was not connected
with the Lancet study.
In 2005, Dr. Simonsen, who was then at the National Institute
of Allergy and Infectious Diseases in Bethesda, Md., published a paper in The Archives of Internal Medicine that found something
odd: even though the percentage of older people who got an annual flu shot more than tripled from 1980 to 2001, there was
no corresponding drop in the death rate. That paper included one of the
first estimates of how many deaths are actually caused by the flu - a number hard to pin down because doctors seldom confirm
flu in their patients with lab tests. Using a statistical model and the best available data, Dr. Simonsen found that influenza
probably causes just 5 to 10 percent of all winter deaths in the elderly. But earlier studies had found that the flu vaccine
cut an elderly person's risk of dying by 50 percent.
"You don't have to do a whole lot of math to realize that
doesn't add up," said Dr. Lisa A. Jackson of the Group Health Center for Health Studies in Seattle, who has also studied the
effectiveness of the flu vaccine in the elderly.
Dr. Jackson at first tried to tease out underlying differences
between vaccinated and unvaccinated elderly people by using medical codes - a numerical shorthand that doctors use to classify
and record what is wrong with their patients. She and other researchers reasoned that patients with codes for cancer or heart
disease, for example, might be very sick, thus skewing the results. When they adjusted for those codes, however, the differences
between the vaccinated and unvaccinated groups became even more pronounced. The vaccine looked even more protective.
It was Michael L. Jackson's thesis project, at the University
of Washington, that revealed the flaw in using the codes to differentiate patients. For
the project, Mr. Jackson (no relation to Lisa Jackson) and three other researchers spent almost three years reading medical
charts and examining X-rays. They discovered that health-conscious people were more likely to get medical codes for things
like heart disease and cancer simply because they went to the doctor more often. But when Mr. Jackson adjusted for measures
of frailty - things like lung function, whether people needed help bathing or dressing, and what kinds of medications they
took - he found that vaccination had little effect on older people's risk for pneumonia, the most dangerous complication of
That finding has a biological basis. Vaccines work by priming
the immune system to recognize and respond to incoming threats. Because the immune system slows down with age, older adults
do not respond as well to vaccines as younger adults. A recent study by
Dr. Wilbur H. Chen and colleagues at the Center for Vaccine Development at the University of Maryland School of Medicine found
that elderly participants needed four times the amount of antigens given in a standard dose of the flu vaccine to have the
same kind of immune response as healthy adults under 40. They presented their findings in May at the Annual Conference on
Vaccine Research in Baltimore.
Despite these findings, Dr. Shay said the C.D.C. had no
plans to change its vaccine recommendations, though he added that the agency had financed studies to look for more effective
influenza vaccines for the elderly.
Dr. Simonsen, the epidemiologist at George Washington,
said the new research made common-sense infection-control measures - like avoiding other sick people and frequent hand washing
- more important than ever. Still, she added, "The vaccine is still important. Thirty
percent protection is better than zero percent."