Emerging tick-borne disease
Wednesday, 03.24.2010, 12:44pm (GMT+3)
Stories of environmental damage and their consequences
always seem to take place far away and in another country, usually
a tropical one with lush rainforests and poison dart
frogs. In fact, similar stories starring familiar animals are unfolding
all the time in our own backyards -- including
gripping tales of diseases jumping from animal hosts to people when
ecosystems
are disrupted. This time we're not talking hemorrhagic
fever and the rainforest. We're talking tick-borne diseases and the
Missouri Ozarks. And the crucial environmental
disruption is not the construction of roads in the rainforest, it is the
explosion
of white-tailed deer populations. An interdisciplinary
team at Washington University in St. Louis has been keeping a wary
eye on emerging tick-borne diseases in Missouri for
the past 20 years. Team members include ecologists Brian F. Allan and
Jonathan M. Chase, molecular biologists Robert E.
Thach and Lisa S. Goessling, and physician Gregory A. Storch. The team
recently
developed a sophisticated DNA assay, described in the
March 2010 issue of Emerging Infectious Diseases, that allows them to
identify which animal hosts are transmitting pathogens
to ticks. "This new technology is going to be the key to understanding
the transmission of diseases from wildlife to humans
by ticks," Allan says.
Missouri has three common species of ticks. The
black-legged tick (Ixodes scapularis) that carries Lyme disease
is found here, but is far less common than in other regions of the
country. Missouri also has
American dog ticks (Dermacentor variabilis),
which carry Rocky Mountain Spotted Fever, but again this is a less
frequently encountered species. The most common tick
is Amblyomma americanum, called the lone star
tick because the adult female has a white splotch on her back. It is a
woodland species originally
found in the southeastern United States whose range
now extends northward as far as Maine. Until recently, this tick, which
is an aggressive and indiscriminate biter, was
considered a nuisance species, not one that played a role in human
disease.
Then in 1986 a physician noticed bacterial clusters
called morulae in a blood smear from a critically ill man that looked
like those formed by bacteria in the genus Ehrlichia
(named for the German microbiologist Paul Ehrlich). At the time Ehrlichia
were thought to cause disease only in animals.
The bacterium was later identified as a new species, Ehrlichia
chaffeensis, and the disease was named human ehrlichiosis. In 1993 E.
chaffeensis DNA was found in lone star ticks collected from several
states. Ehrlichiosis typically begins with vague symptoms that mimic
those of other bacterial illnesses. In a few patients,
however, it progresses rapidly to affect the liver, and may cause death
unless treated with antibiotics. In 1999, a second Ehrlichia
species was identified as an agent of human disease. The DNA of the
newly identified bacterium was also found in lone star
ticks. Gregory A. Storch, M.D., the Ruth L. Siteman
Professor of Pediatrics at the Washington University School of Medicine
in St. Louis, led the team that identified the second Ehrlichia
species. The discovery was described in the New England Journal of
Medicine in 1999. Blood samples from patients in the St.
Louis area who might have a tick-borne disease are
still sent to Storch's lab for analysis.
But the erhlichioses weren't the only emerging
diseases the tick was carrying. In the 1980s, reports had started to
trickle
in from Missouri, North Carolina and Maryland of an
illness accompanied by a bulls-eye rash. Called STARI, for southern
tick-associated
rash illness, it resembled Lyme disease but didn't
seem to be as severe. The lone star tick was also incriminated in these
cases. STARI is thought to be caused by a bacterium
named Borrelia lonestari, after its tick vector. "The question,"
says Thach, Ph.D., professor of biology in Arts & Sciences and of
biochemistry and
molecular biophysics in the School of Medicine, "is
where do infectious diseases come from?" "Most seem to come from nature
-- they exist in other animals -- and then make the
leap from animals to people, Thach says." Assuming this model applies
to the lone star tick diseases, what is their animal
reservoir and why are they jumping? Lone star ticks need blood meals
to power their metamorphoses (they go through three
stages: larva, nymph and adult) and egg laying.
They sometimes bite coyotes, foxes and other animals,
but their favorite hosts are wild turkey and white-tailed deer.
Especially
white-tailed deer, which seem to be playing a major
role in maintaining large lone star tick populations and setting the
stage
for tick diseases to jump to people. Fieldwork
conducted by Allan, Ph.D., a post-doctoral research fellow at Washington
University's
Tyson Research Center in the oak-history forests that
grace the rolling hills of the Missouri Ozarks, was reinforcing the
team's suspicions about deer. In forests managed by
the Missouri Department of Conservation and by the Nature Conservancy,
Allan was looking at the effect on tick numbers of
management practices such as selective logging and prescribed burns.
Allan's
results show that management practices sometimes have
counterintuitive effects on tick numbers. For example, he reported in
the Journal of Medical Entomology in September 2009
that prescribed burns increase tick numbers and human risk of exposure
to lone star tick diseases. To make sense of this
counterintuitive result all you need to do is follow the deer. A
prescribed
burn leads to a flush of new plant growth. Deer, which
are selective browsers, are attracted by the tender greenery. They
flood into the burn sites, and drop blood-sated ticks
as they browse.
Although deer were looking shady, the case against
them was still largely circumstantial. Could the scientists get
definitive
evidence? Allan found a way. He read about an assay
that had been developed in Jeremy Gray's lab at University College
Dublin
to identify animal reservoirs of Lyme disease. ("There
are twice as many cases of Lyme disease in Western Europe as there
are in the United States," says Thach, "and there is a
lot of Lyme research being done there.") Allan asked Thach whether
his lab would be willing to develop a similar assay
for the lone star tick diseases. "With my colleague Lisa Goessling,"
Thach
says, "we developed the technique here and used it to
analyze the ticks Brian brought in from the woods." "The technology
for identifying mosquito blood meals has existed for
some time," Allan says, "because they take many blood meals over a short
period of time, so the blood is usually still fresh
when you capture them. And they keep coming back for another meal, so
it's very easy to capture them. It's much harder to
get blood from a tick, which usually takes only one blood meal per life
stage," Allan continues. "By the time we capture the
tick eight months to a year may have elapsed. The tick has had a long
time to digest that blood, so there may be only a tiny
amount of DNA left -- if there's any."
The team does two assays on the tick DNA: one to
identify pathogenic bacteria and the other to identify the animal that
provided
the blood and with it the bacteria. The first step in
the assay is to pulverize the ticks to release the DNA, which is then
amplified using a procedure called the polymerase
chain reaction, or PCR. This provides enough DNA for identification.
Following
amplification is a step called reverse line blot
hybridization. Probes, which are short sequences of DNA unique to a
bacterium
or to a host animal, are deposited in lines on a
membrane. The membrane is then rotated, and the products of the PCR step
-- tagged with a chemiluminescent (light-generating)
dye -- are laid down in lines perpendicular to the probe lines. Wherever
two lines cross, DNA from the tick sample mixes with
probes for either bacterial or animal DNA. If the two match, the
molecules
will bond, or hybridize. When the membrane is later
washed, tick-sample DNA that has not hybridized washes off. DNA that has
hybridized sticks and shows up as a chemiluminescent
spot on the membrane. Reading the spots, tells the scientists which
bacteria
the tick was carrying and which animal provided its
last blood meal.
Assay results showed that most of the nymphal lone
star ticks infected with E. chaffeensis fed upon a white-tailed
deer in the larval life stage. "So deer are definitely a primary
reservoir for this bacterium," says
Thach. "But we also found some kind of squirrel --
which we have more recently identified as the common gray squirrel --
and
what appears to be some kind of rabbit." In general,
the results suggest deer are probably "weakly competent reservoirs" for
the tick diseases, meaning that ticks that bit deer
stood only a small chance of picking up one of the pathogens. On the
other
hand, deer have huge "reservoir potential," because
there are so many of them. The bottom line: a sprinkling of deer is ok;
crowds of deer are a problem. Are the bacteria that
cause the new tick-borne diseases truly new or have they existed for a
long time in wildlife reservoirs like the white-tailed
deer without causing human disease? "We don't know the answer," says
Allan, " but my guess is these tick-borne diseases are
probably being unleashed by human-mediated environmental change."
By human-mediated environmental change he means deer
protection, the human behaviors that have led to an explosion in
white-tailed
deer populations. "Some state agencies plant food
plots for deer, we've created deer forage in the form of crop fields and
suburban plantings, and we've taken away almost all of
their predators -- except cars," Allan says. To be sure, white-tailed
deer were once nearly eliminated from the state. In
1925 there were thought to be only 395, according to the Missouri
Department
of Conservation. The hunting season was closed that
year and again from 1938 through 1944, and deer were re-located to help
reestablish them in the state. In 2009, Lonnie Hanson
of the Missouri Department of Conservation estimated the herd at 1.4
million. Nationwide the pattern is similar. Nobody is
sure how many deer there are, but estimates range from 8 to 30 million,
levels everyone agrees are excessive. "If you had to
point to one factor that led to the emergence of tick-borne diseases
in the eastern United States, it would have to be
these unnaturally large populations of deer," Allan says.
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