In case you missed it: Part 1 of this series explored the importance of Lyme disease research for human and veterinary medical science. Lyme disease experts Drs. Sam R. Telford III and Alan G. Barbour explained the central role the mouse model has played in past research milestones and future potential breakthroughs Below is Part 2 (of 2).
THE ECOLOGICAL APPROACH
Researchers like Telford are concerned as much with the environmental factors associated with vector-borne illness as they are by the stages of infection and the development of effective treatments. Preventing tick bites by either reducing tick populations or by promoting personal protection can be more effective in reducing the number of cases—in both people and pets—than pre-infection vaccines or post-infection antibiotics.
This is partially because diagnosis can be tricky. Symptoms of Lyme disease closely resemble those associated with other more common illnesses and conditions, including at least four other deer tick-transmitted infections. A notable exception: the EM skin lesion, or the bullseye-shaped rash, that often signifies the presence of the Lyme disease bacterium. Researchers in 2007 wrote, “The occurrence of EM lesions in infected humans has been estimated at approximately 60%. However, it is likely that this figure is grossly underestimated, owing in part to the concealment of the lesion by skin tone or the presence of hair, in addition to a lack of recognition on the part of the patient or physician.” As one might imagine, Lyme disease is also difficult to diagnose in dogs, because the symptoms often overlap with those attributed to other conditions. Animals may experience “generalized pain, start limping, or stop eating. Lameness can appear suddenly, shift from one leg to another, and even disappear temporarily. Some describe it as ‘walking on eggshells.’”
According to the Centers for Disease Control and Prevention (CDC), reported incidents of Lyme disease in the United States have steadily increased since the mid-1990s. In 2015, the most recent year in which data was assembled, there were nearly 300,000 confirmed cases, and nearly 400,000 probable cases. In the northeast, Lyme disease has become an acute public health problem, especially in areas like Nantucket, Massachusetts where about 15-20 percent of residents have been infected.
Telford has advocated for the reduction of the reproductive host—deer—from regions where the deer tick is endemic, as a means of reducing tick density. He explained that each female deer tick lays up to 2,000 eggs, and deer are the hosts upon which they usually acquire their bloodmeal (which is needed to lay eggs). However, deer reduction is an intervention that may not be acceptable to some communities. Other long term interventions, such as an experiment to interfere with the Lyme bacteria’s life cycle, have been supported by researchers including Kevin Esvelt, assistant professor of biological engineering at the Massachusetts Institute of Technology.
The proposed study was detailed in the New Yorker earlier this year:
Esvelt and his team would begin by vaccinating their mice and sequencing the DNA of the most protective antibodies. They would then implant the genes required to make those antibodies into the cells of mouse eggs. Those mice would be born immune to Lyme. Ultimately, if enough of them are released to mate with wild mice, the entire population would become resistant. Just as critically, the antibodies in the mice would kill the Lyme bacterium in any ticks that bite them. Without infected ticks, there would be no infected people.
This work is an extension of the early studies in lab mice and white-footed mice that demonstrated why the Lyme disease vaccine is effective and how it works. It represents a novel ecological approach to curbing the spread of infectious disease, and requires additional research with animal models and regulatory review before implementation on Nantucket.
Barbour explained that some researchers have suggested a different ecological approach—vaccinating the white-footed mouse in its natural habitat, which, theoretically, could reduce the risk of zoonotic infection in humans. “We vaccinate wild animals like raccoons to prevent people and their companion animals from becoming sick with rabies,” he said, cautioning that before we engage in this intervention strategy for Lyme disease, the research community must understand as best it can the white-footed mouse and its response to Lyme disease infection, as well as to the vaccine. “Of course, this first has to be studied in the laboratory with animal models. It’s inconceivable that anyone would just go out and do that in the field, just as it’s inconceivable that someone would administer a drug to people without first testing it on animals.” This is not to suggest it won’t happen soon. Telford, with his team at Tufts, is now seeking USDA approval to deploy a vaccine in the field that they have tested extensively.
OVERCOMING HURDLES TO IMPROVE HEALTH AROUND THE WORLD
Tick season is in full swing, and experts warn that it might extend into other seasons and threaten new regions as climates heat up and become more hospitable to white-footed mice. The likelihood that this will lead to an increase in the number of new Lyme disease cases, for both people and their dogs, strengthens arguments about the need for additional research to better understand, treat, and prevent infection.
Scientists face obstacles in the lab, but also from restrictions in funding and unsteady public support for ecological and biomedical research. They also must contend with efforts by groups opposed to animal research, who threaten further progress while failing to account for, by way of example, the extraordinary advancements in the medical understanding of vector-borne illness that have resulted from studies with animals, especially mice. As Telford explained, “Animal research continues to allow us to better understand disease and test new methods to reduce the burden of ill health, globally as well as in our own backyard.”