By David N. Leff

Picture this scenario for a virtual Western movie. It might be titled "High fever in the high country."

The story opens with a couple hiking in the Rocky Mountains — say, scenic Oregon, Idaho or Colorado. As the early spring night begins to fall, they come upon a deserted rustic cabin, in which they light a fire and spread their sleeping bags. In the morning, each remembers the minor itch of a mosquito bite.

But a mosquito it was not.

A week or so after leaving the area, both experience sudden chills, followed by fever spiking at 102 to 104 degrees Fahrenheit. Then their heartbeats begin to race, their heads to hurt severely, plus they experience vomiting and pain in muscles and joints.

After three to five days of this misery, the fever and other symptoms vanish as abruptly as they came, and the stricken hikers feel they are out of the woods. No such luck.

Following a week of restored health, the disease strikes again, and these relapses recur repeatedly for up to a dozen spaced episodes, with severity gradually subsiding after each attack.

Could this be Lyme disease? Not likely, as no multicolor, bull's-eye rash at the tick-bite site — hallmark of Lyme — accompanied their distressing symptoms. Nor did a blood test reveal the Borrelia burgdorferi spirochete specific to Lyme disease.

Rather it turned up a spirochete of a slightly different stripe — Borrelia hermsii — which inflicts relapsing fever (RF), a tick-borne and louse-borne infection with a venerable past.

Hippocrates, say medical historians, was the first to mention the scourge of RF, over two millennia ago.

Now cut back to that rustic mountain cabin.

Under its floorboards, a colony of chipmunks had spent the winter hibernating. With warmer weather, they woke up and departed, leaving behind a sizeable population of rodent-tropic ticks (Ornithodoros hermsii).

"With the rodents gone," explained medical entomologist Tom Schwan, "the ticks got warmed up, became hungry, and started moving around at night looking for a meal of mammalian blood. A person who's breathing," he continued, "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." Schwan is acting head of the Laboratory of Microbial Structure and Function at the National Institutes of Health's Rocky Mountain Laboratories, in Hamilton, Mont.

RF Bugs Feed Swiftly; Lyme Ones, Slowly

"The hard-shelled ticks that transmit Lyme disease," he told BioWorld Today, "feed on their host for three to eight days." In contrast, "the soft-bodied ticks that transmit relapsing fever take a blood meal in 10 to 90 minutes They can remain alive and infectious for years without feeding," he observed.

Tick-borne RF is rarely life-threatening, Schwan pointed out, whereas the louse-borne variety "has killed hundreds of thousands of people down through the ages." In World War I, he said, "RF was one of the deadly pathogenic triad that included typhus and trench fever.

He cited 1996 statistics listing some 16,000 cases of Lyme disease in the U.S., but fewer than 100 of RF. Schwan added that many cases go undiagnosed, and that common antibiotics can abort the oscillating infection.

Curiously, he observed, the northern Idaho city of Coeur d'Alene, with its tourist-attracting lake, is a hotbed of RF. Schwan and his colleagues analyzed 182 cases of probable RF in the Pacific Northwest over the past 18 years, and "we found the highest number in Coeur d'Alene, for a reason we don't know. There must be some specific ecological conditions around that lake."

Another unknown in the RF equation is why its symptoms switch on and off from tick to host and back again.

Schwan is senior author of a paper in today's Science, dated June 19, 1998, which adds a piece to this puzzle. Its title: "Bloodstream- versus tick-associated variants of a relapsing fever bacterium."

He and his colleagues had previously turned to recombinant screening of DNA libraries for spirochete outer-surface variable membrane proteins (VMP) that react with human immune defenses. They identified two of these serotypes, VMP 7 and VMP 8.

In B. hermsii, Schwan also found, "the antigen is an enzyme, which is not found in the Lyme disease B. burgdorferi. The RF microbe uses it to make lipid components of its cell wall." Schwan uses it as a diagnostic enzyme.

"In the human disease," he said, "during the febrile phase, 99 percent of the protein is all from the same serotype. Then it crashes and disappears, only to come back seven days later with a different VMP serotype. That antigenic variation," he pointed out, "allows the organism to escape the human immune defenses of its host, by switching.

"Eventually, after numerous on-and-off episodes, the disease is cleared by the relatedness in the serotypes, which builds up over time."

Mice Sort Out Spirochete Surface Proteins

In his Science-reported experiment, Schwan infected one group of mice with spirochetes carrying the VMP 7 serotype, and another cohort with VMP 8. Then he turned two groups of ticks loose to feed on blood from each set of rodents, and so infect them.

When the ticks grew hungry again, the investigators allowed 50 individual ones to feed on 50 individual mice, and infect each of them with VMP 7. Another 50 got VMP 8. Then, by means of antibody identification, the team determined "these proteins all get turned off during infection in the tick, and a different stable type of protein gets produced in their place.

"Finally, when the spirochete is transmitted back to a mammal, that tick-specific protein gets turned off again, and the microbe goes back to producing the very same VMP that it was expressing when the tick ingested it from its last blood meal."

Schwan is now preparing to pursue "this unique morphological change in the spirochete" by creating defective spirochetes. "We will attempt to knock out their VMP genes, so that they're unable to disseminate in the tick," he said.

"Knowing how these spirochetes behave during tick feeding," Schwan concluded, "will increase our ability to design more effective strategies for both diagnosis and protection." *