Tom G. Schwan, Ph.D., acting chief of the RML Laboratory of Microbial
Structure and Function, and B. Joseph Hinnebusch, Ph.D., staff fellow in
the lab, co-authored the report published July 19 in the journal
Science. RML, based in Hamilton, Mont., is part of the National
Institute of Allergy and Infectious Diseases (NIAID).
"A large number of proteins on the surface of the relapsing fever
spirochete vary during infection in mammals," explains Dr. Schwan. In
fact, it's the spontaneous changes in these proteins during human
infection that allow the microbe to periodically escape immune
detection, leading to a relapse of symptoms. "In our mouse studies,"
says Dr. Schwan, "we found that these proteins all get turned off during
infection in the tick and a different stable type of protein gets
produced in their place. But when the spirochete's transmitted back to
a mammal, that tick-specific protein gets turned off again and the
microbe again produces that very same variable membrane protein that was
being produced when the tick ingested it."
Decreasing the temperature, the RML scientists discovered, can trigger
the change. "One likely cue that promotes this switch is the drop in
temperature that occurs when the spirochete moves from a warm-blooded
animal to a tick," Dr. Schwan notes.
Their observations of Borrelia hermsii, the spirochete that causes
relapsing fever, can be extended to other Borrelia species, says Dr.
Schwan, including B. burgdorferi, the causative agent of Lyme disease.
"For us," he says, "it's a way to get a handle on the whole genus."
For example, they now know that when either Lyme disease or relapsing
fever spirochetes are transmitted to a mammal via tick saliva, the
spirochetes turn on similar surface proteins. "We think this family of
proteins is an important part of the spirochete in all Borrelia,
possibly in their transmission from arthropod to mammal," says Dr.
Schwan. Knowing how these spirochetes behave during tick feeding will
increase scientists' ability to design more effective strategies for
both diagnoses and protection, he notes.
In addition, Dr. Schwan - who has spent his entire research career
studying ticks and the diseases they cause - says relapsing fever can be
easier to study than Lyme disease. "The ticks that transmit relapsing
fever are easier to rear than those that transmit Lyme disease," he
notes. "Transmission is easier to document and observe, and infection
in the laboratory animals is easier to detect."
Currently, the RML scientists are exploring the protein's exact function
to determine the role it plays in transmission. By manipulating the
genome of the relapsing fever spirochete, they can inactivate the gene
that makes the protein. "We want to know," explains Dr. Schwan, "if we
knock out the gene making this protein associated with transmission, is
Relapsing fever is not a nationally reportable disease. However, Dr.
Schwan and his colleagues at the Centers for Disease Control and
Prevention and elsewhere conclude in a recent review of 182 case records
that the disease is underrecognized and underreported, and often
mistaken for Lyme disease.
People with tick-borne relapsing fever suffer cyclical high fevers and
other symptoms such as headache and pain in the joints, muscles or
abdomen that easily can be mistaken for a severe flu. These episodes
usually last several days, alternating with periods when the symptoms
cease. In most patients, the infection responds to treatment with
antibiotics such as penicillin, tetracycline or erythromycin.
While the hard-shelled ticks that transmit Lyme disease feed on their
host for three to eight days, the soft-bodied ticks that transmit
relapsing fever take a blood meal in 10 to 90minutes. "They feed at
night, they feed rapidly, and generally people don't even know they've
been bitten by these ticks. People might wake up in the morning and
think they've been bitten by a mosquito," says Dr. Schwan.
Tree squirrels, chipmunks and other wild rodents found in coniferous
forests in the higher elevations of the Western United States serve as
the primary reservoirs for the relapsing fever spirochete. The
soft-bodied ticks that associate with these rodents can remain alive and
infectious for years without feeding.
Human cases of illness tend to peak in the warmer months, since if it's
too cold, the ticks can't move. But the disease can occur year-round.
A common scenario for human infection is to have a tick population
established with rodents who've made their home in rustic mountain
cabins, explains Dr. Schwan, in attics, walls, basements or under the
floor. "If the rodents die off, leave or hibernate, the ticks look for
other hosts. In winter, people often will stay in these cabins and warm
them up for a week. The rodents are not active, the ticks get warmed
up, and they become hungry and start moving around looking for a food
source. A person who's breathing is basically a carbon dioxide
generator. The ticks actually orient to a carbon dioxide gradient, and
this is one of the ways they find their hosts."
NIAID supports biomedical research to prevent, diagnose and treat
illnesses such as AIDS and other infectious diseases, asthma and
allergies. NIH is an agency of the U.S. Department of Health and Human
Press releases, fact sheets and other NIAID-related materials are
available via the NIAID Web site at http://www.niaid.nih.gov.
TG Schwan and BJ Hinnebusch. Bloodstream- versus tick-associated
variants of a relapsing fever bacterium. Science 280:1938-40 (1998).
MS Dworkin, DE Anderson, TG Schwan, PC Shoemaker, SN Banerjee, BO Kassen
and W Burgdorfer. Tick-borne relapsing fever in the Northwestern United
States and Southwestern Canada. Clinical Infectious Diseases 26:122-31