For the past 20 years, the tick-borne bacterium that causes Lyme disease has been a thorn in the side of medical science. While doctors are locked in bitter debate over how to diagnose and treat the ailment, researchers estimate that as many as 200,000 Americans are infected each year.
When a vaccine went on sale earlier this year, it looked as if Lyme's terrible legacy might be ending. More than 850,000 doses later--at $49 per dose to doctors--Smith-Kline Beecham Pharmaceutical's LYMErix is causing as much confusion as celebration. Some doctors worry that the much-publicized vaccine may induce serious arthritis and other Lyme-like reactions in a significant minority of users. Others fret that they'll have an even tougher time detecting the disease in patients who take the vaccine, which SmithKline says is at least 78% effective after three shots.
The controversy is just the latest twist in a baffling disease. In the current Journal of the American Medical Assn., researchers note that accuracy varies substantially among the 53 tests for Lyme that are approved by the Food & Drug Administration. "To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests," the authors warn.
The need for better testing and treatment for this public health scourge grows more imperative each year. Lyme disease was not identified until 1975, when doctors saw a rash of cases in Lyme, Conn. They realized the infection, caused by the Borrelia burgdorferi bacterium, was spread by deer ticks. Connecticut now has the highest incidence, followed by Rhode Island and New York, according to the Centers for Disease Control & Prevention. But the disease has been reported in 48 states.
Infection is thought to occur most often when people are bitten during the tick's nymph stage, when it's no larger than a pinhead and particularly hard to detect. Some people develop a slowly expanding bull's-eye rash near the bite, often suffering fatigue, fever, headaches, muscle aches, and joint pain as well. But about 20% don't have any symptoms for months. While most patients recover after a 28-day course of antibiotics, Lyme can sometimes lead to severe arthritis, facial palsy, neurological problems, brain inflammation, and heart problems, all of which can persist years after the initial infection.
Jody L. Ring of Greenwich, Conn., is exhibit A for the problems surrounding treatment. When she became infected seven years ago, doctors diagnosed her symptoms as depression and chronic fatigue syndrome. Four years and a dozen doctors later, Ring was finally tested and treated for Lyme disease. She went through intravenous and long-term antibiotic treatment after the standard four-week drug course failed to work. Ring says she looked into taking LYMErix, which is recommended for existing sufferers to avoid reinfection, but decided against it after several doctors told her they "wouldn't even take it themselves or vaccinate people with it" because not enough is known about possible complications.
ONLY THEORY? The uncertainty arises from the potential side effects that could afflict patients who aren't properly screened. About 20% to 30% of the population carries a gene called HLA-DR4. When infected with Lyme disease, these patients are more likely to develop treatment-resistant arthritis and other chronic symptoms. Because the vaccine triggers an immune response against the Lyme bacteria, it might set off those same symptoms in patients with the HLA-DR4 gene.
SmithKline executives insist that such worries are more theory than reality. "We've looked through the data and found nothing," says David M. Stout, SmithKline Beecham's president for North America. Of the 5,469 adults who received the vaccine in clinical trials, investigators say, the number who developed arthritic complaints was similar to that of the placebo group. But the trials excluded people with joint-swelling diseases, immune deficiencies, certain heart problems, and chronic Lyme-related symptoms, in case their conditions confused the outcome. Little is known about the vaccine's effect on those groups.
An advisory committee did end up recommending that the FDA approve the vaccine, but the committee voiced concerns about long-term safety. "I would hold off on vaccinating anybody with an ongoing clinical illness," says Robert T. Schoen, clinical professor of medicine at Yale University and a committee member who voted for approval. "Given that this is a new vaccine, it will do best if we are thoughtful about using it."
BETTER TESTS. Still, few would dispute that a vaccine is crucial. Vijay K. Sikand, a co-investigator in the LYMErix study, blames the controversy on a lack of understanding. While adverse reactions are "theoretically possible," he says, "they haven't happened yet." More importantly, says Sikand, initial studies show the vaccine to be at least 78% effective against initial infections and 100% effective against the severe symptoms that might show up years later. He notes that LYMErix appears to be even more effective at the same dose in children and that new studies advocate a two- to six-month immunization schedule for adults.
Pasteur Merieux Connaught usa of Swiftwater, Penn., says a vaccine that it is now developing could be even better. It claims its vaccine, called ImuLyme, is 92% effective. The vaccine has not yet been approved.
At the moment, the best advice may be to simply mirror the clinical trials for LYMErix. Healthy adults between 15 and 70 who have no history of arthritis or immune problems might decide a vaccination is critical if they live in high-risk areas--and if they are screened for the HLA-DR4 gene. But Karen Vanderhoof-Forschner, who chairs the Lyme Disease Foundation in Hartford, says the larger issue is the lack of a good diagnostic test.
Currently, the Lyme test cannot be administered until four to six weeks after a person is bitten--and, as JAMA reported, even then the disease can be hard to detect. "Without a good test, how do you prove the vaccine works?" asks Vanderhoof-Forschner. "We need to stop the name-calling and work on the basic science." Until then, danger will continue to lurk in the backyard.