June 19, 1998 Scientists at the Rocky Mountain Laboratories (RML) report that the corkscrew-shaped bacterium that causes tick-borne relapsing fever switches surface proteins when it moves from a tick into a mammal or vice versa. Their finding, they say, could lead to an improved blood test for diagnosing the illness, one that might help clinicians distinguish relapsing fever from its better known relative, Lyme disease, in the Western United States where both diseases are endemic.
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 June 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 transmission blocked?"
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 Services. ### 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 (1998).
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