In Wake Of Lyme Disease Vaccine For People, Mice May Be Next In Line For Shots

A Michigan State University disease ecologist leads a novel ecological approach to battle Lyme disease. It proposes that ground zero is the forest floor, and immunizing the tiny critters there offers hope to ultimately reduce the number of dangerous tick bites that infect some 23,000 people in 2002 in the United States. The work is published online this week in the Proceedings of the National Academy of Science.

"There is more than one way to try to reduce Lyme disease risk besides relying just on developing vaccines for humans. We also should try ways to intervene in nature because we can potentially help more people by reducing the risk at its source," said Jean Tsao, an assistant professor of fisheries and wildlife, who designed the experiments to evaluate the effectiveness of vaccinating mice.

The research explores reducing the number of infected ticks that transmit the Lyme disease pathogen by vaccinating mice in the forest, thus placing fewer people at risk. The study also paints a more accurate – and surprisingly complex – picture of how Lyme disease is distributed in a forest, and how all forests are not the same.

"It shows us that with many emerging infectious diseases originating from animals, no one approach is likely to be a cure-all," Tsao said. "Diseases like this demand you think at the wildlife-community level, not just at the patient level."

Lyme disease is caused by bacteria that multiples and incubates in the bodies of many animals found in the forest. Ticks suck blood from the infected animals, transforming themselves into Lyme delivery systems.

The tick's two-year life cycle allows it to feast first on small animals, such as mice, shrews and raccoons, and later on larger animals such as deer. Humans fall into the mix as they cross paths both in the wilderness and even in yards where wildlife treads.

A vaccine for humans was developed to prevent Lyme disease, but has been withdrawn from the market due to complaints of potentially vaccine-caused arthritis. Reducing the deer population has proven difficult in many areas for practical and political reasons.

Targeting mice is important because they are responsible for producing many infected nymphs, the young tick stage that presents the greatest health risk for people.

Tsao decided to take an experimental view of the Lyme disease cycle in nature to get a better understanding of how the Lyme disease pathogen distributes itself among the forest animals. She spent summers in 1998 and 2001 with a team of field assistants in 12 different forested sites in Connecticut, running what amounted to a medical clinic for mice

The mice were trapped live in the one- and two-hectare forest plots. After anesthetizing mice, the researchers would weigh each mouse, draw blood and count ticks. Mice often are loaded with ticks – she's seen as many as 60 stuck to just one ear of a mouse. All mice were tagged and vaccinated with the Lyme vaccine, then rehydrated with an apple slice and released.

In the end, she ended up with medical records of nearly 1,000 mice. "I had to keep track of every mouse, because I wanted to know how many booster shots we gave it, how it responded to the vaccine, and whether the vaccine had failed," she said.

The vaccine's beauty in the field is that it kills the bacteria in any ticks that feed off the immunized mouse, leaving that tick unthreatening to humans.

After immunizing roughly 55 percent of the mouse population over the course of the two studies, researchers saw an overall 16 percent reduction in the prevalence of nymphal infection at locations in which mice had been given vaccine versus placebo. This translates to a possible 27 percent reduction in nymphal infection had all the mice been vaccinated.

But the study also showed that in many forests, vaccinating mice alone wouldn't be enough. Different forests have different mixes of wildlife, and the conventional wisdom of the mice-deer-tick cycle is too simple to effectively battle Lyme disease. The development of an oral vaccine would allow for greater vaccination coverage of both mice and other animal hosts.

"We've learned we shouldn't naively ignore other hosts – shrews, chipmunks, robins, and maybe others," Tsao said. "Unexpectedly, other hosts contribute more to maintaining bacteria than we had thought. Other people might be deterred by the complexity. But just because nature is complex shouldn't mean we shouldn't try to design a solution."

Other authors on the paper, "An ecological approach to preventing human infection: vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle," are J. Timothy Wootton at the University of Chicago; Durland Fish at Yale University School of Medicine; and Jonas Bunikis, Maria Gabriela Luna and Alan Barbour at the University of California at Irvine.

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The study was primarily funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.