As a new generation of adolescent deer tick enjoys its first blood meal,
scientists in the United States and abroad continue to focus their
research efforts on understanding and preventing Lyme disease. Ticks
infected with the bacterium Borrelia burgdorferi cause more than
10,000 cases of Lyme disease in the U.S. each year, according to the
Centers for Disease Control and Prevention. Scientists specializing in
immunology, epidemiology, parasitology, and even rheumatology are all
pursuing lines of research they hope will lead to a better understanding
of how B. burgdorferi causes Lyme disease and how people can best
SIZE MATTERS: Deer ticks -- vectors of
Borrelia Burgdorferi -- are half the size of the common dog
tick, which is not associated with Lyme disease.
Researchers studying disease prevention cover a lot of ground,
whether they're crawling through the underbrush tracking infected ticks
in the field or conducting large-scale clinical trials to determine the
efficacy of Lyme vaccines in humans. At the same time, immunologists and
microbiologists are trying to determine how B. burgdorferi
interacts with the human immune system to cause Lyme disease. Armed with
funding from the National Institutes of Health, Lyme researchers are
trying to unravel the basic biology of B. burgdorferi-its natural
ecology, its genome sequence, and its slippery coat of
among other areas of investigation.
The life cycle of the Lyme disease vector-the deer tick Ixodes
scapularis-is fairly well known. In the spring, nymphal deer ticks
that survived the winter seek out tasty mammals for their first
postlarval feast. Though adult female I. scapularis ticks prefer
deer, the poppy-seed-sized nymphs will also feed on white-footed deer
mice or humans. And any tick that fed last season on a mouse infected
with B. burgdorferi-a corkscrew-shaped bacterium known to
microbiologists as a
pass Lyme disease on to a human this year.
In the northeastern United States, particularly in Rhode Island,
Connecticut, and Westchester County and Long Island n New York,
scientists estimate that half the deer-tick population may harbor agents
that cause illness, including Lyme disease and ehrlichiosis-another
bacterial infection characterized by flu-like symptoms (story on page
VEXING VECTOR: Ixodes scapularis, the
carrier of Lyme disease -- the most common insect-borne disorder in
Lyme disease is named after a community on the coast of Connecticut.
The first cases in the U.S. were identified in 1975 by physicians Allen
Steere and Stephen Malawista, researchers at Yale University School of
Medicine. Scientists, however, believe that B. burgdorferi has
been around for thousands of years. Examining well-preserved museum
samples, parasitologist Sam Telford of the Harvard School of Public
Health and David Persing at the Mayo Foundation in Rochester, Minn.,
have identified B. burgdorferi spirochetes in North American
white-footed deer mice collected in the late 1800s.
But if the
spirochete has lived in North America as long as humans, why didn't
on the continent before the 1970s? Did B. burgdorferi become more
infectious? No one knows. In fact, many fundamental questions about how
spirochete causes disease in humans are unanswered, says Alan
Barbour of the University of Texas Health Science Center in San Antonio,
author of Lyme Disease: The Cause, the Cure, the Controversy
(Johns Hopkins University Press, 1996). At the most fundamental level,
scientists have yet to determine exactly how B. burgdorferi
causes disease in humans. By studying how the immune system reacts to
spirochete, immunologists and microbiologists may begin to
understand why some infected people experience mild symptoms and others
wind up with a chronic illness.
UNANSWERED QUESTIONS: Exactly how the Lyme
spirochete causes disease in humans is unknown, observes Texas'
EHRLICHIOSIS AND LYME
DISEASE: PEAS IN A POD?
As the most common tick- or insect-borne disease in the U.S., Lyme
disease research is well supported by the federal government. As a
whole, NIH spent about $13.5 million on Lyme disease research in 1995,
with the bulk of the funding coming from the National Institute for
Allergy and Infectious Diseases. This level is expected to increase to
just over $14 million in 1996.
|Although most cases of Lyme disease respond to antibiotic
treatment, occasionally the symptoms persist, and even worsen. A
number of researchers are investigating why some patients wind up
with chronic Lyme disease.
Co-infection may have something to do with it, notes Sam Telford,
a parasitologist at the Harvard School of Public Health in Boston.
According to Telford, when they feed on infected white-footed mice,
deer ticks can pick up the bacterium that causes human granulocyte
ehrlichiosis (HGE), the
spirochete that causes Lyme disease, or the protozoan that
causes human babesiosis, an infection of red blood cells. And ticks
with multiple infections can pass along all three diseases with a
single bite (S. Telford et al., Proceedings of the National
Academy of Sciences, 93:6209-14, 1996).
"People don't realize that the tick that transmits Lyme disease
also carries two other organisms because it feeds on infected
white-footed mice," says Telford. "But I don't see why people are so
surprised, because we've seen this kind of co-infection in Europe
for many years," he adds.
Telford and his colleagues collected Ixodes scapularis
ticks from the backyard of a Nantucket patient with HGE. They found
that an outdoor enthusiast walking through the woods for an hour
could encounter perhaps a dozen ticks infected with Borrelia
burgdorferi, the agent responsible for Lyme disease, and another
four ticks that carried HGE. That same stroller
also run into two ticks that harbor both disease-causing bacteria.
Ehrlichiosis and babesiosis share the flu-like symptoms
characteristic of Lyme disease-the muscle aches, fever, headache,
and fatigue. In addition, patients with babesiosis may also
experience chills, night sweats, even depression. But patients
infected with B. burgdorferi develop a distintive circular
rash around the site of the tick bite. Still, because the risk of
co-infection is high, Telford suggests that physicians who suspect
that a patient has contracted one of these tick-borne diseases test
for all of them.
Without a proper diagnosis, physicians will be unable to treat
these distinct diseases, notes Telford. Although each can be cured
by antibiotics, Lyme disease responds best to penicillins,
ehrlichiosis to tetracycline, and babesiosis to antimalarial
medications. "These illnesses may linger because they're never
diagnosed. So the disease is not treated at all," he says. Left
untreated, chronic Lyme disease can damage the heart and nervous
system. And ehrlichiosis can be fatal in some cases.
Co-infection with a second tick-borne agent may also explain why
Lyme disease varies in severity from patient to patient, says
Telford. In a five-year study of 1,156 people living on Block Island
in New England, Telford and his collaborators found that patients
with both Lyme disease and babesiosis show more symptoms and are
sick longer than patients with either infection alone (P. Krause et
al., JAMA-Journal of the American Medical Association, 275:1657-60,
1996). Co-infection with babesiosis or HGE may mean the difference
between feeling under the weather and being unable to get out of bed
for a patient with Lyme disease, says Telford.
An ounce of prevention beats a trip to the pharmacist for a cure.
Avoiding tick bites remains the most reliable way to avoid Lyme
disease, ehrlichiosis, and babesiosis, stress Lyme disease
researchers. Telford prescribes insect repellents and nightly tick
Though most cases of B. burgdorferi infection can be
eliminated easily by a short course of antibiotics, Lyme disease can be
disabling if left untreated. Scientists are searching for answers to how
the relatively small numbers of bacteria (1,000 microbes per milliliter
in infected humans) can cause excessive inflammation, and why the
spirochetes localize to certain tissues, including the joints, the
heart, and the brain. They suspect the key to the mystery lies on the
in the collection of
that coat its outer membrane.
Patients with Lyme disease experience flu-like symptoms-aches, fever,
nausea, joint pain. When the spirochetes first get under the skin, they
mark their point of entry with a characteristic bull's-eye rash. Left
unchecked, the B. burgdorferi bacteria will work their way into
the bloodstream and head off to other organs. In late-stage Lyme
disease, a month or two after infection, the spirochetes take up
residence in the heart or the joints, where they cause inflammation.
Others settle in the brain, where the body's immune system can't reach
them as easily.
Working with the related
B. turicata, Barbour has found that bacteria that wind up in the brains
of immune-deficient mice differ by only a single protein from the
bacteria that remain in the blood. The protein, which shows homology to
protein OspC from a variety of B. burgdorferi strains, may allow
spirochete to establish the kind of long-lasting brain infection
that underlies lingering Lyme disease, he theorizes.
According to Barbour, B. burgdorferi lacking its outer-surface
(including OspA, OspB, OspC, and OspD) is easily killed by the blood's
complement system. Several groups of researchers are currently
B. burgdorferi loses when it is kept in culture conditions for
too long. When the
is raised without contact with a mammalian
is unable to infect mice. And, according to microbiologists James
Carroll and Frank Gherardini of the University of Georgia, it may also
lose OspD and a handful of previously unidentified
(J.A. Carroll, F.C. Gherardini, Infection and Immunity, 64:392-8,
Many researchers believe that the secret to B. burgdorferi's
infectivity and inflammatory capacity lies in the interaction of its
immunological system. Yale researcher Stephen Barthold, a
veterinarian and professor of comparative medicine who developed the
first mouse model of Lyme disease, studies the expression of B.
throughout various stages of the
spirochete's life cycle. He finds that during the early stages of
infection, B. burgdorferi avoids immune detection by decreasing
its expression of
or cloaking its expressed
under a layer of slime. "It's using some sort of stealth-bomber-type
mechanism," he says. Or, using another diversionary tactic called
can pinch off bits of its membrane in order to release its
Explains Barbour: "It's
like a bacterial Star Wars defense program," in which
During the early stages of infection, perhaps while the
is still inside the tick, B. burgdorferi switches on a whole new
that may help it adapt to life in its mammalian
according to Barthold. These so-called in vivo expressed antigens may
spirochete invade tissues or elicit inflammation in the joints (S.W.
Barthold et al., Laboratory Investigation, 74:57-67,
TINY CREATURES: In size order, the three tick
feeding stages are nymph, larva, and adult, shown next to a U.S.
Although they can offer educated guesses, researchers are still
unsure what roles the
of B. burgdorferi play in infection and disease. A group of
protein chemists and crystallographers at Brookhaven National Laboratory
in Upton, N.Y., and the State University of New York, Stony Brook, are
taking a more structural approach. John Dunn and Cathy Lawson purified
and crystallized OspA-a
protein that B. burgdorferi expresses when it lives in the midgut
of the tick. The structure
offer some clues to how the protein functions, says crystallographer
Lawson. Further, because the Lyme disease vaccines now being tested in
humans contain OspA, Lawson says, "it would be nice to know what the
protein looks like." The researchers presented their results at the
seventh International Conference on Lyme Borreliosis, held in San
Francisco late last month. The biennial meeting draws more than 400 Lyme
researchers from around the world.
LYME DISEASE RESOURCES
Understanding when each
protein gets expressed may be important for developing an effective
vaccine for Lyme disease. The OspA vaccine can combat infection only
when OspA is present on the
of B. burgdorferi, when the
is still in the gut of the tick. Once the tick takes a blood meal, the
gets rid of its OspA in preparation for the transfer to its mammalian
Thus, the OspA-based vaccines cannot prevent Lyme disease once an
animal, or a human, has been infected with B. burgdorferi. In
fact, the OspA vaccine, which protects mice against a challenge with the
spirochete, destroys B. burgdorferi while it's still inside
the feeding tick, says Barthold.
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Two large-scale, Phase III clinical trials of OspA vaccines in humans
are being conducted by researchers at Connaught Laboratories in
Swiftwater, Pa., and SmithKline Beecham in Philadelphia. Some 10,000
individuals received injections of lipidated OspA protein; the
researchers will soon analyze the data to determine whether the vaccine
protected recipients against Lyme disease. The results from the Phase II
clinical trials indicate that the vaccine is
but may cause local irritation at the site of the injection.
This irritation may be one of the problems facing researchers
developing a Lyme vaccine. Because the disease can be cured with
antibiotics or simply avoided by limiting exposure to ticks, Barbour
thinks that the public may demand a vaccine that has absolutely no side
effects. To further complicate matters, researchers don't know how often
people would need to be re-vaccinated. To remain protected, a person
must have a certain level of circulating OspA antibody in the blood,
says Steere, now at the New England Medical Center and Tufts University
School of Medicine in Boston.
But that opens questions about who should get vaccinated. "Does Uncle
Charlie get vaccinated when he visits you in Westchester County [in New
York]?," asks Durland Fish, an entomologist and epidemiologist at Yale.
"It'd be like preparing for a trip [overseas]."
BIRTH CONTROL: Yale's Durland Fish advocates
tick population management as a disease-prevention strategy.
While several groups of researchers continue to pursue a Lyme
vaccine, others think that the key to preventing the disease lies in
controlling the ticks themselves. "The bottom line? You need to get rid
of the ticks," says Fish, who preaches the power of pesticides. "It
amazes me that people would prefer to have a foreign antigen injected
into their bodies rather than have a chemical sprayed onto their lawns,"
With tick territories expanding along with deer populations, Fish
advocates using insecticides to stop ticks from moving into new areas.
Other researchers at the University of Rhode Island are developing
biologicals-searching for ways to use the ticks' natural enemies,
including certain fungi, to keep their population under control.
Nature may present researchers with other clues for tick control. In
the Northeast, tick populations fluctuate naturally-rising and falling
from year to year. Why? "We don't have a clue," acknowledges Fish. But
the number of reported cases of Lyme disease seems to correlate with
number of infected ticks, he notes.
After spending 11 years tracking B. burgdorferi in mice and
ticks on Nantucket, scientists are no closer to being able to make
yearly predictions on the potential for incidences of Lyme disease. But
Telford says that the number of cases of Lyme disease does correlate
with the weather: Rain usually keeps people indoors, thus limiting their
While scientists continue to work toward developing effective ways of
preventing B. burgdorferi infection through vaccines or
tick-population management, they advise the public to use common sense
to avoid getting bitten by a hungry deer tick. For those heading for the
hills or the woods, they recommend using insect repellents, wearing long
sleeves, and tucking trouser cuffs into socks. "It really works," says
In fact, the trouser-tuck is even de rigueur for parasitologists
beating the bushes for ticks: "I figure I've crawled through the bushes
for eight- or ten-thousand hours looking for ticks," asserts Telford,
"and I've never come down with anything."
Karen Hopkin is a freelance science writer based in New York City and
senior producer for National Public Radio's "Science Friday." She
created the "Studmuffins of Science" 1996 calendar and is online at