In the summer of 1975, children from the rural towns near Lyme, Conn., began developing an odd type of arthritis. Yale rheumatologists Allen Steere, M.D., and Stephen Malawista, M.D., were called in to investigate, and they quickly determined that the strange seasonal flare-up had all the markings of an infectious disease. Eventually, Steere and other Yale investigators discovered that a corkscrew-shaped bacterium known as a spirochete was responsible for the condition they dubbed Lyme disease.

Malawista, Steere and colleagues went on to show that humans contracted Lyme disease after being bitten by deer ticks, which pick up the bacterium themselves from wild mice. Yale scientists went on to develop successful antibiotic treatments for the disease that prevent the painful arthritis and debilitating neurological problems that occur in some people.

But these stunning early successes of Yale scientists in the diagnosis and treatment of Lyme disease have not been matched by equal gains in prevention. Residential development in rural areas has placed more people in contact with ticks. A Lyme disease vaccine proved unpopular with consumers and was taken off the market. The disease now ranks as the most common tick-borne illness in the United States, with the number of new infections rising 35-fold since 1982. In 2002, over 23,000 cases were reported to the Centers for Disease Control and Prevention (CDC).

Entomologist Durland Fish, Ph.D., of Yale’s Department of Epidemiology and Public Health, decided to revisit the vaccine strategy, but instead of humans he targeted the white-footed mouse, a key player in the spread of Lyme disease.

Working in the woods outside New Haven, Fish and his colleagues captured nearly 1,000 wild mice and injected them with the Lyme vaccine. As reported in the Proceedings of the National Academy of Sciences, the next year the researchers found lower rates of Lyme infection in both mice and ticks in the study areas.

“This is the first field study to show that we can decrease natural infection rates for a tick-borne disease by immunizing wildlife,” says Fish. “Obviously it’s not feasible to catch all the mice in a large area and inject them, but an edible vaccine, something you could incorporate into bait, should work as well.”

Lyme disease prevention expert Joseph Piesman of the CDC hopes that Fish’s results will stimulate more studies of wildlife vaccination. “We need more options for controlling and preventing Lyme disease, and these ecological, host-targeted approaches are very important,” Piesman says.

Newborn deer ticks are infected with the Lyme disease bacterium during a single, summertime feeding on a mouse, and the bacterium spends the winter inside the tick’s gut. In spring, when the ticks feed on humans, the bacterium can be released into the bloodstream, causing Lyme disease.

According to professor of medicine Erol Fikrig, how the bacterium sets up residence in the tick during winter has been a mystery, but late last year, Fikrig’s group wrote in the journal Cell that they had discovered a receptor that serves as a docking station in the tick gut for the Lyme disease bacterium.

“If you manipulate the ticks so that they no longer have this receptor, you reduce the spirochete,” says Fikrig, who envisions the creation of a receptor-blocking vaccine that would prevent ticks from carrying the Lyme disease bacterium.