This summer, researchers from many universities have been venturing into the woods looking for a bloodsucking arachnid that’s responsible for infecting humans and, often, their dogs with a range of illnesses including Lyme disease: the back-legged tick, or “deer tick”. Despite significant strides in the medical understanding of diseases carried by vectors—organisms that transmit infections either between humans or from animals to humans—a few remaining questions have scientists stumped. For example, it remains unclear why some patients treated for Lyme disease still feel poorly after completing antibiotic regimens prescribed to defeat the bacteria that made them sick.
Meanwhile, it’s been widely reported that an increase in the number of confirmed cases of tick-borne illness has followed in tandem with an increase in the arachnid’s population, especially in New England and mid-Atlantic states. What does this mean for people who wish to protect themselves and their pets?
Two prominent Lyme disease experts weighed in on the significant milestones in research that have been reached, and they also shared some of the exciting new frontiers in medical discovery that may lie ahead. Research ecologist and epidemiologist Sam R. Telford III is a professor of vector-borne infections and public health at the Tufts University Cummings School of Veterinary Medicine. Alan G. Barbour is a professor of medicine, microbiology, and molecular genetics at the University of California-Irvine School of Medicine and the author of, “Lyme Disease: Why It’s Spreading, How It Makes You Sick, and What To Do About It (2015).”
Both scientists credited the studies with animal models that have drastically improved the body of medical knowledge related to Lyme disease, leading to more effective treatments and risk-reduction methods. They agreed that new approaches to curbing the rate of infection—intervention strategies that may improve the health of people, families, and communities around the world—will rely in large part on animal studies.
Telford has studied ticks and vector-borne illness for 30 years. He said the pathogenesis of Lyme disease, or the means by which host organisms become sick after infection, is well understood thanks to researchers who successfully replicated the disease in laboratory mice in the early 1990s. Telford was involved in the clinical testing of a vaccine that successfully prevented Lyme disease infection in humans—a recombinant vaccine produced through DNA technology—which he explained was first tested in mice, then successfully used in human clinical trials, and adapted for veterinary use to protect dogs. One of the most successful of the canine Lyme disease vaccines is virtually identical to the human vaccine, which is no longer available. “The human work predated veterinary work and was the direct result of the mouse model,” Telford said.
In two studies of data collected from coastal areas, Lyme disease infection was more common in dogs than in people. And research shows the bacteria’s prevalence in dogs correlates with, to an extent, the level of Lyme disease risk for human populations: “Our results support the hypothesis that dogs can be used as part of a regional surveillance system for Lyme disease to determine risk of disease to humans as well as dogs,” the study’s authors concluded.
They explained that because dogs usually give blood samples annually, and because they generally have more prolonged contact with outdoor environments than their human counterparts, dogs can serve as part of a system of active surveillance to track with more precision the number of infected deer ticks.
Determinations of the regionally-specific risk of Lyme disease have significant implications for work by researchers like Telford, who rely on accurate data to develop ecological solutions to curb the rate of infection among humans and pets. Research on the prevalence of infection in dogs helps to better define risky areas. In turn, we help protect the health of our canine companions by the fruits of those early laboratory studies of Lyme disease immunity in mice.
THE MIGHTY MOUSE MODEL
The medical research community believes that mice may unlock an even more comprehensive body of knowledge regarding vector-borne illness. “Genetically determined murine [mouse] models are useful for providing a deeper insight into Lyme disease pathogenesis,” wrote the authors of a study that concluded bacteria isolated from different animal species can cause Lyme infection through different patterns of distribution, leading to the disease’s characteristic lesions (dermatological, cardiac, and arthritic) in mice. “Mice have been extensively investigated as an experimental mouse model because the mouse immune system is by far the best understood.”
It also happens that the stages of Lyme disease infection in mice very closely mimic the disease’s progression and associated symptoms in human patients. “B. burgdorferi infection in laboratory mice has many clinicopathologic features in common with Lyme disease in humans,” wrote the authors of a study that linked differences in the severity of arthritic lesions to different bacterial serotypes, or variations in the strain. Furthermore, in a different study that examined mild and severe arthritis in mice with Lyme disease (8 days and 20 days, respectively, post-infection), researchers argued that the various pathways of inflammatory response in the animal subjects “provide a basis upon which to examine a broad spectrum of inflammatory severities, including chronic arthritis, in humans. These animal models also increase knowledge and understanding of the basic infectious process and assist in developing strategies to prevent infection and disease in humans.”
Arthritis is not the only symptom associated with untreated Lyme disease infection, however, and Lyme disease is not the only vector-borne illness to which humans are susceptible. In fact, these days Telford is collecting ticks and using mice to study different strains of the Powassan virus, which can cause severe neurological symptoms and encephalitis (or swelling of the brain) in human patients. Though uncommon, the number of severe encephalitis cases attributed to the tick-transmitted infection are on the rise, especially in areas with large numbers of deer ticks. “I’ve heard of four cases in the last 10 months,” said Telford. “We need to figure out why we are starting to see that.”
Despite the availability of safe and effective antibiotic regimens for Lyme disease, some patients do not feel “back to baseline” after treatment. Barbour explained that because white-footed mice generally tolerate the infection reasonably well, maintaining relatively good health and reproducing successfully even without treatment, the mouse model, along with studies involving other animals, model might “lead to new clues about what is different for some human patients who don’t feel better.”
Part 2 (of 2) in this blog series will examine some of the ecological approaches to mitigating the risk of Lyme disease infection, diagnostic challenges faced by healthcare practitioners, and additional commentary from Drs. Telford and Barbour about intervention strategies that could improve public health.