As Maryland wraps up its worst flu season in three years, a small army of researchers is working on a vexing problem: why flu shots so often don't help the elderly.
No matter how many people are vaccinated and what recipe drug makers use to formulate the flu vaccine each year, it generally works in only 30 percent to 40 percent of those over 65 - compared with 80 percent to 90 percent of younger adults, experts say.
Doctors gauge a vaccine's effectiveness by examining blood levels of the antibodies our bodies produce after receiving it. They say older bodies have more trouble producing the antibodies than younger ones, even with a push from flu vaccine, so they're working on a more potent version of today's shots for older patients.
Flu has hospitalized at least 800 people in Maryland since the season began in October, about 30 percent of them children, according to state health officials. The season runs from October to May.
"This was a very active flu season," said Rene Najera, an epidemiologist with the Maryland State Department of Health and Mental Hygiene.
Maryland hospitals reported roughly 2,250 lab-confirmed cases in each of the two weeks after Feb. 10 - identified by the Centers for Disease Control and Prevention as the peak of this year's flu season.
This was the first year that the state's hospitals reported such figures, making comparisons with previous years impossible, Najera said. The number of flu cases began to drop sharply by mid-March, he said.
But nationwide, flu continues to take a heavy toll, hospitalizing 200,000 people each year, killing 36,000 and causing fever, fatigue, headaches and other symptoms for up to 20 percent of the population each year, according to the CDC. The numbers remain high despite more vaccinations each year.
Improvements are slow in coming because the flu virus is a constantly evolving target. The recipe for each year's vaccine is an educated guess based on the type of viral strains common in Asia at the close of the previous season.
Scientists believe the virus migrates to North America from the Far East. Overall, flu vaccine is usually 70 percent to 90 percent effective, but it was only 44 percent effective this year because the virus evolved a step beyond what international health experts expected.
"Strains for last year were expected to circulate again this year, but the virus mutated," Najera said.
Like flu itself, vaccination is an evolving science. In February, the Centers for Disease Control and Prevention updated flu shot recommendations for youngsters by adding children 6 months old and over. Previously, the CDC had recommended shots only for adults.
Increasingly, researchers are looking for flu vaccines to help the elderly because they are most likely to develop pneumonia and other life-threatening complications if they catch the flu.
"About 90 percent of the people killed by the flu are the elderly, so those are the people we want to help," said Dr. Wilbur Chen, an infectious disease specialist at the University of Maryland School of Medicine.
But it is the hardest group to help.
A major obstacle is that as we age, our immune systems become less responsive to medications and vaccines, a cost of growing older that scientists call immune senescence. The decline starts in our 40s and 50s and accelerates when we reach our 70s, experts say.
"We actually don't understand why the immune system senesces, but we know that it does," said Dr. Janet McElhaney, a geriatrician with joint appointments at the University of Connecticut Health Center and the University of British Columbia.
When the flu virus enters the body, the immune system launches a two-pronged attack, generating antibodies that neutralize virus particles and producing T cells that recognize viral signatures on the surface of infected cells and attack them. Vaccines stimulate the production of antibodies and T cells.
But among the elderly, T cells become less able to recognize the virus on the surface of the infected cells and less capable of mounting a response, McElhaney said.
"T cell function begins to deteriorate around age 50 and real problems develop in the late 60s and 70s," McElhaney said.
Chen recently conducted a study comparing how elderly volunteers given standard doses of flu shots compared with those given doses with four times the quantity of antigens that fight the flu. Their average age was 74.
He analyzed blood samples taken from 26 volunteers who got the standard dose and 23 who got higher doses during the 2004-2005 flu season. A control group of 14 adults between the ages of 18 and 40 was given the standard dose.
The results showed the higher doses produced almost as many flu fighting antibodies among the elderly volunteers as standard doses given to younger volunteers.
"It seemed to erase some of the effects of aging," Chen said.
Dr. Geoffrey Gorse, an infectious disease specialist at the St. Louis University School of Medicine, found the same benefits in a study of 4,000 elderly patients who had the same concentrations of higher dose flu vaccine formulated for the 2006-2007 flu season.
Chen and Gorse presented their findings this month at the National Foundation for Infectious Diseases vaccine research conference in Baltimore. Gorse's work was funded by Sanofi Pasteur, a flu vaccine manufacturer. Chen's study was part of a larger study funded by the National Institutes of Health.
Chen, McElhaney and other experts emphasize that the elderly should get a flu shot at the start of the season each fall - but not more than one.
That's because effective vaccines for the elderly will require not only stronger doses that produce more antibodies but entire reformulations that stimulate T cell production, McElhaney said.
"I think we've got a long way to go on this," she said.