Getting Lyme disease to take a hike

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Now that summer is here, many people are hitting the hiking trail. But before you head for the wilds, you should take some special precautions, especially if you live in a part of the country where Lyme disease is prevalent.

It's been nearly two decades since medical detectives discovered that an outbreak of what looked like juvenile rheumatoid arthritis in Lyme, Conn., was actually a spirochetal (bacterial) infection spread by tick bite. Today we know enough about the tick and its infective cargo to avoid Lyme disease or stem its effects early. FDA regulates several products used to help diagnose and to treat this complex illness, but doctors sometimes still have a hard time diagnosing it.

Three Stages
Although most people can recall the tick bite that transmitted the bacteria responsible for their Lyme disease, I of 3 cannot remember being bitten. This is not surprising, because the responsible tick (of species Ixodes dammini or Ixodes pacificus) is as small as a poppy seed. It is often not seen or felt. If the tick stays attached and maintains contact with a person's blood for at least six hours, bacteria called Borrelia burgdorferi can travel from the tick's gut to the person's bloodstream. These bacteria are of a type called spirochetes, named after their spiral shape.

The bacteria soon migrate to specific areas of the body where they later may produce symptoms: within the skin at the bite site, in the synovial fluid of the joints where bones meet, and into nerve tissue.

The first sign of disease, in up to 80 percent of cases, is a distinctive large, red rash called erythema chronicum migrans, appearing at the site of the bite three to 30 days after contact. The lesion expands and may develop a clear area in the center, like a bulls-eye. Then, flu-like symptoms may set in, including headache, muscle ache, fatigue, and joint pain. If a physician suspects Lyme disease at this point-based on symptoms, the characteristic rash, the geographic area, and recollection of a tick bite-the patient may begin a course of antibiotic drugs that can stem further symptoms. With antibiotics, the rash usually clears up in a few days; otherwise, it disappears in about a month.

The second stage of Lyme disease occurs a few weeks or months following the tick bite, as bacteria spread beyond the skin. The body starts to produce antibodies against the bacteria, which, when detected in a person's blood, indicate exposure and form the basis of a tentative diagnosis. At this point, Lyme disease can be distinguished from other conditions, such as fibromyalgia (muscle pain) and chronic fatigue syndrome, which produce similar symptoms.

In this stage, 50 to 80 percent of patients develop arthritis. Lyme arthritis differs from rheumatoid arthritis in that it tends to come and go and affects two or three joints, rather than producing an all-over achiness. And while osteoarthfitis can affect only a few joints, the presence of the other symptoms may suggest Lyme disease. New skin outbreaks, usually smaller than the first, may appear at this time.

The Borrelia bacteria can affect the nervous system in the second stage of Lyme disease. The brain, its membranes, or peripheral nerves may become inflamed, producing severe headache and a stiff neck. Inflammation of the cranial nerves may cause facial paralysis, lasting weeks or months. There may also be memory loss, difficulty concentrating, and changes in mood or sleep habits. About 15 percent of people with Lyme disease not given antibiotics in the first stage go on to develop nervous system symptoms.

About 8 percent of untreated Lyme patients develop heart problems, such as heart block, inflammation of the heart or surrounding tissue, and irregular heartbeat. These problems may produce symptoms of shortness of breath and dizziness.

The third stage of Lyme disease occurs about six months after the initial rash. Arthritis persists in about 50 percent of untreated patients, and may cause extreme swelling, particularly of the knee. In most patients, the arthritis eventually clears up. Only 5 to 10 percent are left with the continuous joint pain of chronic Lyme arthritis. Some evidence suggests that these people are genetically predisposed to overreact to the Lyme bacterium, extending the normal inflammatory response to infection or injury.

Late-stage Lyme disease may also produce continued neurological symptoms and rash.

Hot Spots
More than 40,000 cases of Lyme disease in 48 states have been reported to the national Centers for Disease Control and Prevention since surveillance began in 1982. The disease, however, is still concentrated in certain areas where Lyme spirochetes, ticks, mice, and deer are common.

Each year, the geographic areas where spirochete-infected animals and Lyme disease occur enlarge. In the 1970s, in New England the illness was restricted to Cape Cod, Nantucket, Martha's Vineyard, and the southwest comer of Connecticut. Today, it is found in many parts of Connecticut, western Massachusetts, New Hampshire, and Maine. On the East Coast, one is most likely to contract Lyme disease on Block Island in Rhode Island, Martha's Vineyard and Nantucket Island in Massachusetts, eastern Long Island and Westchester County in New York, and in Connecticut, where epidemiologists identified the first cases. The illness is also common in wooded areas of the mid-Atlantic states, and in Wisconsin, Minnesota, and northern California.

The bacteria that cause Lyme disease have also spread up the Hudson River from Westchester, with the first cases identified in Adirondack State Park in upstate New York last summer. Lyme disease has been reported in all states except Alaska and Montana. However, the number of reported cases may be an overestimate, because other conditions associated with rash and joint pain may be incorrectly diagnosed as Lyme disease.

Biology of the Bug
Transmission of the spirochete that causes Lyme disease is a biological back-and-forth between ticks in different stages of their life cycle and hosts, which are usually mice and deer. The tick feeds only once during each of its three stages-larva, -lymph and adult. A larva typically picks up Lyme spirochetes in late summer from ingesting the blood of a white-footed field mouse (in the Northeast) or a wood rat (on the West Coast). The bacteria are harmless to the rodents. The next spring, the larva becomes a nymph, still housing spirochetes in its gut. A nymph that bites a human transmits the bacteria. Nymphs also bite mice, perpetuating the chain of infection by depositing bacteria in the rodents' bloodstreams, where future ticks will pick up the infection. In the fall, the ticks, now adults, prefer to feed on deer. The deer do not support the bacteria, but provide a mating site for the ticks.

Diagnosing Lyme Disease
Diagnosing Lyme disease can be challenging, because a patient complaining of flu-like symptoms and fatigue could have any of a number of conditions. Further, not all Lyme disease patients develop the same set of symptoms. And because the bacteria cannot be easily isolated from blood, and culturing them from skin lesions until recently was difficult, diagnosis may be based only on signs and symptoms.

"When Lyme disease first appeared, it was diagnosed only in a certain geographical area. As physicians became aware of the disease, there was a flurry of overdiagnosis," says Renata Albrecht, M.D., of FDA's division of antiinfective drug products, which regulates antibiotic drugs, including those used to treat the disease.

Diagnostic tests for Lyme disease are not as definitive or specific as scientists would like them to be. Besides detecting antibodies to the bacteria that cause Lyme disease, these tests detect antibodies the body manufactures in response to infection by any of several other microbes, including those that cause mononucleosis or syphilis. In some instances, the tests also detect the antibodies produced in certain autoimmune disorders, such as rheumatoid arthritis and systemic lupus erythematosus. A specific diagnostic test for Lyme disease requires identifying a part of the spirochete unique to that species of bacterium, which would stimulate the immune system to produce an antibody unique to Lyme disease.

Researchers at the National Institutes of Health's Rocky Mountain Laboratory in Hamilton, Mont., discovered such an antigen, a protein called p39. "The protein is found in nearly all isolates of Lyme spirochete, but not in other species. Plus, it is quite reactive with serum from patients with late-stage Lyme disease. It appeared to have good potential as a diagnostic test to detect specific antibodies to the Lyme spirochete," says Tom Schwan, Ph.D., who, with co-workers, used recombinant DNA technology to mass-produce p39.

FDA cleared for marketing three versions of a p39-based diagnostic kit for Lyme disease in 1992. "There was considerable testing in outside labs to show how it would fare," adds Schwan. But like any antibody-based test, the p39 test is not reliable until four to six weeks after infection-the time it takes for the body to produce antibodies. Also, the test does not distinguish between someone who was recently infected and someone who harbors antibodies from a previous infection with the spirochete.

Still, scientists are investigating whether using the polymerase chain reaction (PCR), a technique that can make millions of copies of a specific gene (piece of DNA) in just a day, can make diagnosing Lyme disease more precise. A report on this research by Allen Steere, M.D., Jame J. Nocton, M.D., and co-workers at the New England Medical Center in Boston appeared in the Jan. 27, 1994, New England Journal of Medcine.

Lyme disease diagnosis is often more o a problem in geographic areas where the illness is rare, because doctors sometimes think it too unlikely to consider. This happened to Melissa Blatnik, 20, who lives near Cleveland, where Lyme disease is rarely seen. She had been very ill for a year, incurring $50,000 in bills for procedures such as MRIs and CAT scans, which would have been unnecessary had she received a correct early diagnosis. It wasn't until her mother saw a television program about Lyme disease describing symptoms identical to hers that Melissa began to suspect Lyme disease-a hunch that was later confirmed by her doctor's diagnosis.

Treatment
FDA has not approved any treatment specifically for Lyme disease, but doctors have prescribed commonly used antibiotics since about 1980.

"Well-known spirochetes, such as those that cause syphilis, are treated with amoxicillin. So physicians have extrapolated from that" and prescribe that drug to treat Lyme disease, says FDA's Albrecht.

For FDA to specifically approve a treatment, a large-scale, carefully controlled clinical trial would need to be submitted for review, she adds. But since useful drugs are already available, pharmaceutical manufacturers lack incentive to conduct such a trial.

Physicians most commonly prescribe oral doxycycline, amoxicillin or erythromycin. When oral antibiotics don't work or a patient has severe arthritis or neurological symptoms, the physician administers intravenous ceftriaxone or penicillin G. Doctors do not, however, prescribe antibiotics for tick bites if the patient has no Lyme disease symptoms. This is because not all ticks carry the spirochete-only 50 percent of ticks are infected in the most heavily infested areas.

One problem with using antibiotics to treat Lyme disease is that treatment can curtail the body's production of Lyme spirochete antibodies, which may make a person less resistant to repeat infection. "I know someone in Connecticut who got Lyme disease three times. Each time he got a rash, and treated it promptly, so no antibody response developed," says Schwan.

"Researchers are also interested in seeing if there are different strains of the spirochete. If there are, a person could develop immunity to one strain, then go somewhere else and encounter a different strain that isn't killed by the antibodies," he adds.

Vaccines
A vaccine is usually made from a killed microbe, or part of it, that signals the immune system to mount an attack. A Lyme disease vaccine containing a protein from the surface of the spirochete, called Osp A, is being evaluated in humans. It is currently being tested for efficacy in preventing Lyme disease in high-risk northeastern populations.

Vaccine test results in mice published in the June 1992 issue of the Proceedings of the National Academy of Sciences suggest that this particular vaccine has a double effect, protecting the mice while also stemming the spread of infection by ticks. In the experiment, uninfected mice were given the vaccine, then exposed to ticks carrying the Lyme bacteria. Vaccinated mice not only remained free of infection, but when the ticks bit them, the antibodies the mice had made after stimulation with the vaccine killed the spirochetes in the ticks too! Mice given a placebo instead of the vaccine became infected. The researchers, from Yale University and Harvard University School of Public Health, hope that Lyme disease may be controlled by adding the vaccine to the plants and water supplies that wild rodents consume. If rodents can no longer harbor the Lyme bacteria, then ticks cannot become infected and spread the disease.

Lyme disease may be disabling and painful. Fortunately, there is much you can do to prevent it (see "Prevention Tips"). But if you should pick up one of these tiny ticks and develop symptoms, be sure to see a doctor immediately. Caught early, Lyme disease can be halted if appropriately treated.

Reported Cases of Lyme Disease in the United States, 1992
AK 0
CT 1760
DE 218
DC 3
HI 2
MD 183
MA 212
NH 49
NJ 681
RI 274
States where groups of mice and deer are known to harbor ticks carrying Lyme disease (Source: Centers for Disease Control and Prevention)

PHOTO: A tick.

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By Ricki Lewis, Ph.D.

Ricki Lewis, Ph.D., is a writer in Scotia, N. Y., and a biology textbook author.

PREVENTION TIPS
Health departments in areas where Lyme disease is prevalent offer these tips for preventing infection:

Wear protective clothing in woods and grasslands, and especially where these two areas meet. Wear long pants and long-sleeved shirts that are tight about the ankles and wrists; tuck pants into socks; wear shoes that cover the entire foot; and wear light-colored clothing so that the ticks can be easily seen.

Use repellent containing permethrin or DEET, but don't overdo it; children can have difficulty breathing from too much bug spray.

If you visit the woods, do tick checks when the day is done. Closely check hairy parts of the body, and examine pets, too. Ticks prefer rodents and deer, but will hop onto almost anything warm and furry, and while wild animals can harbor the spirochete without becoming ill, domestic animals do develop symptoms of Lyme disease. (A vaccine for dogs is available.)

If you find a tick, remove it with tweezers, being careful not to squeeze it. Apply antiseptic to the bite area. If possible, bury, bum or flush the tick. Researchers are currently looking at whether applying a topical antibiotic cream can stop the infection right after the bite.

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