Getting Lyme Disease To Take A Hike
by Ricki Lewis, Ph.D.

     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, 1 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 osteoarthritis 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 corner 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, nymph
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 anti-infective 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., James 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 Medicine.
     Lyme disease diagnosis is often more of 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 œPrevention Tipsœ). 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. n

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:
œ    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, burn or flush the tick. Researchers are currently looking at
whether applying a topical antibiotic cream can stop the infection
right after the bite.