Battling Lyme Disease

Many anxiously awaited last summer's debut of LYMErix, the first vaccine against tick-borne Lyme disease approved by the Food and Drug Administration (FDA). Indeed, hundreds of thousands of Americans living in high-risk areas rushed to have the shot, heaving a sigh of relief. For them, the threat of Lyme, an inflammatory disease that affects many body parts, had put fear into most outdoor summer fun. In the late 1990s about 12,500 annual cases occurred in the U.S90 percent of them in only 10 states in the Northeast, Mid-Atlantic, and upper north-central regions and in parts of northwestern California.

But now it seems that some of the relief LYMErix gave residents in these areas may have been premature: during the past year, there have been several media reports of patients who developed symptoms of chronic arthritis after receiving the vaccine, raising doubts about its safety. The FDA stands by its decision and holds that the connection between LYMErix and arthritis is unproved. But many people have been left wondering which is worse, the risk of Lyme disease or that of an incurable form of arthritis.

Most cases of Lyme disease are contracted between May and August through exposure to deer ticks (eastern U.S.) and western black-legged ticks (western U.S.) carrying the corkscrew-shaped bacterium Borellia burgdorferi, named after W. Burgdorf, who discovered it in 1982. The ticks themselves become infected early in their two-year life cycle, as larvae or nymphs, when they feed on other infected animals, especially mice. In high-risk areas, about 20 to 50 percent of the ticks are infected.

Most humans pick up the infection from tick nymphs, which can be smaller than the head of a pin and so difficult to see. The nymphs insert their mouthparts into a human's skin and release the bacteria while they are feeding. Their lunch break can last several days, and the infection typically sets in after more than a day--by which time adult ticks have most often been spotted and removed.

The first symptoms usually arise after one or two weeks. They include a characteristic "bulls-eye rash" around the bite and flu-like symptoms, including fever, fatigue, muscles aches and stiff joints. Later, more dangerous symptoms, such as inflammation of the nervous system (encephalitis, meningitis), the heart (myocarditis) and the joints, can follow. But the disease usually responds well to antibiotics, and it is rarely fatal.

A minority of patients, however, develop untreatable chronic Lyme arthritis. Those particularly susceptible have a certain type, or allele, of an important immune molecule called MHCII. For this group, who make up some 30 percent of the population, contracting Lyme disease poses a very dangerous long-term threat. And yet it is this same group that some experts feel may be prone to develop the problems allegedly caused by the vaccine.

What scientists know is that sufferers of chronic Lyme arthritis have high levels of antibodies against OspA, one of the proteins expressed on the outer surface of B. burgdorferi. Researchers have also shown that part of OspA is highly similar to a human protein called LFA-1. And in patients with Lyme arthritis, white blood cells--important agents in all immune reactions--can respond to this human protein in the test tube. This means the arthritis could in fact be the result of an autoimmune reaction caused by OspA.

The Lyme disease vaccine consists of the very same protein, OspA. Once injected, the immune system produces antibodies against it, protecting the body in case of an infection. But stimulating the immune system against OspA might be adding fuel to the fire for vaccine receivers who are at risk of developing Lyme arthritis in the first place.

So why wasn't this possibility explored before the vaccine reached the market? In fact, prior to the vaccine's approval researchers did show that the same number of vaccinated and unvaccinated people in clinical trials developed arthritis. Still, the Advisory Committee on Immunization Practices recommended that the vaccine not be given to the people with a history of Lyme arthritis. Perhaps they should have included in this group everyone with the "risky" MHCII allele.

Only further research--and wider vaccine usage--will show whether the vaccine does pose a significant risk that the clinical trials missed. In the meantime, the safest option for most people is probably avoiding tick bites, even if that means leaving your shorts and sundresses in the closet this season.