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Veterinary Medicine Offers Potential as New Tool to Reduce Lyme Disease

blacklegged tick (Ixodes scapularis) questing

Blacklegged ticks (Ixodes scapularis) acquire the pathogen that causes Lyme disease from mice and other small mammals. A new study shows that a drug for protecting pets from ticks could be deployed in rodent baits to interrupt the host-to-vector transmission cycle. (Photo by James L. Occi/Armed Forces Pest Management Board via Flickr, CC BY-NC-ND 2.0)

By John P. Roche, Ph.D.

Lyme disease causes a significant public health burden, leading to an estimated 476,000 cases per year in the U.S. The disease is caused by a bacterium, Borrelia burgdorferi, which is spread in eastern and central North America by blacklegged ticks (Ixodes scapularis). The primary hosts of the bacterium in this region are the white-footed mouse (Peromyscus leucopus) and the deer mouse (Peromyscus maniculatus).Lyme disease is an expanding problem, and thus control strategies are critical to reduce its growing medical and economic costs.

To explore a potential new control strategy, researchers at the University of Montreal and the Public Health Agency of Canada examined the following question: If Peromyscus mice are dosed with fluralaner, a medication for tick and flea control on dogs, will the number of ticks on the mice be reduced? Their study was published in August in the Journal of Medical Entomology.

Reducing Lyme disease risk involves a variety of interconnecting goals, including reducing the density of ticks in the environment, reducing the number of ticks in the environment that are infected with the Lyme disease bacterium, reducing human exposure and risk of transmission of Borrelia, and preventing human infection using vaccines or antibiotics. This study focused on the first two of these goals by testing whether fluralaner reduces the density of ticks in the environment and the number of infected ticks in the environment when used on small mammals.

Fluralaner offers several advantages as a compound to kill ticks (an acaricide). It is safe for humans and pets, and, after a dog receives a dose, fluralaner kills ticks quickly and continues to kill them for weeks. This makes it highly effective for eliminating ticks that land on an individual animal.

The study, led by Jérôme Pelletier, DVM, a Ph.D. candidate in epidemiology at the University of Montreal, was conducted in the wild in the Estrie region of southern Quebec, Canada. Pelletier and colleagues set up two manipulated treatment zones and one unmanipulated control zone, and each of these zones contained several 75-meter-by-75-meter experimental plots.

In the treatment-zone plots, baits loaded with fluralaner mixed with peanut butter were deployed for six weeks for three summers in July and August. In Treatment Zone 1, the density of baits deployed in 2017 and 2018 was 4.4 baits per 1,000 square meters. In Treatment Zone 2, the density of baits deployed in 2017 and 2018 was 2.1 baits per 1,000 square meters. Animals were also sampled in 2016, but the sample size was too small that year to be statistically usable.

For sampling, the team captured small mammals in each zone two times each summer. Investigators sedated each animal; removed and recorded the number of tick adults, larvae, and nymphs on it; and then released it back into the wild.

In larval sampling, Pelletier and colleagues found that mice in both treatment plots had significantly fewer tick larvae than mice in the control (bait-free) plots. The average reduction in the number of larvae was 68 percent in the lower-density plots and 79 percent in the higher-density plots.

In nymphal sampling, mice in the higher-density plots had significantly fewer tick nymphs than mice in the control plots, with an average reduction of 72 percent. There was no significant difference in the number of nymphs on mice in the lower-density plots versus the control plots.

The potential significance of these results to control efforts lies in the Lyme-disease transmission cycle. Small mammals such as Peromyscus mice are the primary reservoir of Borrelia burgdorferi bacteria in the environment. In the first step of the cycle, a small mammal is infected by a tick that was infected by a previously bitten small mammal. In the second step, another tick feeds on the infected small mammal and becomes infected, a tick that in turn can spread the bacteria to other small mammals—or to humans.

“An acaricidal treatment, such as the bait used in our study,” Pelletier says, “can act on both of these components of the Bburgdorferi cycle by preventing nymphal Iscapularis ticks from transmitting the infection to small mammals and by killing ticks infesting already-infected small mammals.”

These results establish the promise of fluralaner for reducing tick numbers on mice, but two main challenges exist to using fluralaner to control Lyme disease. “The first challenge concerns regulations,” Pelletier says. “When, as veterinarians, we used fluralaner, we used it extra-label for research purposes. But to design a product that would be used widely or that could be marketable, fluralaner would have to be licensed for this purpose.”

The second challenge is cost effectiveness, because fluralaner and other compounds known as isoxazolines are expensive. Pelletier and colleagues are addressing this challenge by developing a mathematical model that would examine the interaction of various factors such as the amount of drug used, the proportion of mice that are treated, and the different tick hosts and Lyme disease bacterium reservoirs. Pelletier says, “We will use this model to forecast what would be the outcome of different treatment-deployment protocols. The goal of the model would be to find scenarios of fluralaner treatment that have the highest impact on the density of Bburgdorferi-infected ticks at the lowest cost.”

The results of this study are promising, but Pelletier emphasizes that this test of the association between deploying baits and the number of ticks infesting small mammals is only the initial step in engineering a new strategy to help reduce Lyme disease. Next steps include determining if reducing the number of ticks on small mammals will lead to a reduction in infected ticks in the environment and determining if a reduction in infected ticks leads to a reduction in human Lyme disease cases.

John P. Roche, Ph.D., is an author, biologist, and science writer dedicated to making rigorous science clear and accessible. He has a Ph.D. and a postdoctoral fellowship in the biological sciences and has published over 200 articles on science. He has served as a scientist and science writer at Indiana University, Boston College, and the University of Massachusetts Medical School and as an editor-in-chief of science periodicals at Indiana University and Boston College.

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