Tick-borne disease – such as Lyme disease, Rocky Mountain spotted fever and babesiosis – rose by 25% from 2011 to 2019 in the United States. Lyme disease cases alone hover around 30,000 a year, up from 22,000 in 2010, according to the Centers for Disease Control and Prevention.
WVU scientists are confronting the issue head-on from angles that include developing vaccines and designing tools that quickly diagnose tick-borne infections. And they’re mostly working in cross-disciplinary teams to take down the tiny but mighty tick.
Beneath the bacteria
Over in the biology department at the Eberly College of Arts and Sciences, Tim Driscoll, associate professor of biology, and his lab are focused on zoonotic diseases, primarily the bacteria that reside in ticks. These bacteria are responsible for diseases like Lyme and are transmitted into mammals, including deer mice, white-tailed deer and humans.
“Bacteria are really fascinating to us,” said Driscoll, an associate professor. “Because our lab is trying to understand the genomes of these bacteria and these pathogens. We’re also studying what makes them pathogens versus what makes other ones not pathogens.”
Rickettsia is a genus of bacteria responsible for a range of diseases including Rocky Mountain spotted fever, a potentially fatal infection. The rickettsiae group includes bacteria very closely related at the genomic level but that cause different pathogenicity in the host, which is why Driscoll’s research team studies it.
“We see large differences between bacteria that are genomically very similar,” Driscoll said.
To find out why, he and his students are looking for rickettsiae in ticks, studying how often the bacteria occur and under what conditions. While rickettsiae can also be transmitted to people, humans don’t perpetuate the pathogens’ life cycle. Therefore, his focus is on the changes that occur in the bacteria as they go between ticks and smaller mammals, which can potentially make them either more or less lethal to humans, a theme that undercuts many diseases, including viruses like COVID-19 and influenza.
“As we interact with the land, that can put us into contact with populations of ticks we might not have been in contact with historically,” Driscoll said. “For example, we carve out parts of the forest to build new subdivisions and we leave islands of trees. Animals like deer mice and small rodents are forced into those little islands, and the ticks also populate them. So we’ve increased ticks’ natural hosts right in our neighborhoods. Kids go out to play, dogs run around and they pick up these ticks.”
Climate change also expands ticks’ natural range, and winters are milder and wetter.
“Ticks are active in the winter much more than 10 or 15 years ago, when we used to have deep, cold winters, with temps in the single digits for weeks,” Driscoll said. “They don't like that because they're cold blooded. They'll go dormant during those long cold spells. Nowadays, we get 40- and 50-degree weather in February, and it gives them a longer time to live, encounter hosts and replicate.
“We don't see the fatalities like we do with something like COVID, but the number of people infected with and suffering from long-term Lyme disease is staggering. People have called it the silent epidemic of this decade.”
Driscoll’s lab has been working with Mariette Barbier’s WVU project in developing targets for Lyme Disease vaccines. They’re exploring the possibility of building on the mRNA vaccine approach that was so successful for COVID-19 and whether they could apply it to Lyme.
“It’s a hard problem, and it’s a long game,” he said. “It may take 10-15 years to try to answer these questions. But I have really good students working on it, and we may be close to having treatment available.”
Put to test
Existing approaches to diagnosing tick-borne infections can involve a symptom-based questionnaire – which might ask if a person has a fever or a rash – and tests that aren’t reliable until at least a few weeks after infection.
Not quick enough?
That’s where a team led by a WVU biomedical engineer enters the fray as they work to ramp up and reimagine how medical professionals diagnose these infections. Soumya Srivastava, assistant professor at the Benjamin M. Statler College of Engineering and Mineral Resources, is developing a tool that more quickly detects tick-borne diseases via a blood sample on a single chip. Srivastava’s model aims to detect disease within one to two weeks after the onset of an infection.
The project was awarded $1.2 million as a joint initiative between the National Science Foundation and the National Institutes of Health. Research will involve cross-disciplinary use of microfluidics, sensors and machine-learning. Those factors will enable improved diagnosis of tick-borne infections via a non-invasive, affordable, quick and user-friendly tool.
After collecting a blood sample from a patient, the tool will analyze the cells. All cells have a set of dielectric properties like permittivity and conductivity that are unique for cell membrane and cell cytoplasm, Srivastava explained. Those properties are heavily dependent on the state of the cell, such as whether it is normal or abnormal.
The unique properties depend on the shape and size of the cell; if the membrane is rough, smooth or leaky; and what is happening within the cell interior.
“We basically are measuring these properties on our microfluidic chip,” she said, “and the electrical signal coming from the sensor will help us determine if there is an infection or not. This technique is known as dielectrophoresis.”
Once a few drops of blood enter the device, an electric field will sort them based on the state, size and shape of the cells. The sorted cells will have a baseline value of capacitance that will show up by the sensor and thus we can conclude the type of infection, Srivastava said.
“Machine-learning is applied to make this tool robust and sensitive to detect multiple infection within few minutes.”
What makes the project more unique is its ability to detect multiple tick-borne infections at once, and in a timely fashion.
“Our platform can detect these diseases early on, within one to two weeks, in under 30 minutes using a portable diagnostic tool,” Srivastava said. “Most tests available currently are symptom-based. If successful, this tool may be useful for a variety of health applications beyond tick-borne diseases.
“Rapid detection could reduce the risk of hospitalization and doctor’s visits and prevent the disease from progressing into a chronic, lifelong condition.”
Vaccine prevention
While ticks are responsible for transmitting a host of diseases, the blacklegged tick – also known as the deer tick – and the western blacklegged tick are the primary carriers of Borrelia, the bacterium that causes Lyme disease.
WVU researchers have been developing a vaccine that would prevent people from contracting the disease. Since the team began their five-year project in 2020, they have established mouse models to study vaccine efficacy and safety. Through RNA sequencing, they are currently examining how pathogens respond in both infected ticks and mice to determine what’s needed for Lyme disease vaccine development.
Researchers hope to identify relevant antigens – substances that cause the immune system to produce antibodies against it – during the infection phases.
“In the next year or so, we should be able to evaluate experimental vaccine efficacy against transmission of the bacterium by ticks,” said Mariette Barbier, associate professor in the School of Medicine’s Department of Microbiology, Immunology and Cell Biology, who is leading the project. “I am particularly passionate about working on this pathogen as it affects our community, and I would love to make a difference in the health of West Virginians.”
Initially, the project was funded with $1.9 million from the National Institute of Allergy and Infectious Diseases. The team has now secured additional funding from the National Institutes of Health and has partnered with Merlin Biotech to evaluate mRNA vaccines as a platform for vaccination against Lyme disease.
“It is also a very complex problem and a great scientific challenge to identify the right components to formulate a protective vaccine against this pathogen,” Barbier said. “It creates unique training opportunities for students at WVU.”
The vaccine will be a preventative measure against Lyme disease, not a treatment. Barbier believes, ideally, the vaccine will be available for all ages to prevent as many infections as possible.
A bite by an infected tick results in a red rash that can emerge on the skin and resemble a bull’s-eye. If untreated, Lyme disease can lead to debilitating conditions such as arthritis, muscle pain, meningitis, and heart and brain inflammation. When detected early enough, infections with Borrelia can be stopped with antibiotics; however, the pathogen can often go undetected, leading to the development of Lyme disease.
A vaccine will be of particular benefit to West Virginians. The CDC categorizes West Virginia as one of 14 states with a “high incidence” of Lyme disease cases and has been declared “endemic” in all 55 counties.
In addition to Lyme disease, other tick-borne illnesses have been reported in West Virginia, including anaplasmosis, ehrlichiosis and Rocky Mountain spotted fever.
The blacklegged tick, along with the lone star tick and the American dog tick, are the primary carriers of most tick-borne illnesses in the United States.
Joining Barbier and Driscoll on the project is Heath Damron, associate professor and director of the WVU Health Sciences Vaccine Development Center.
Hopefully, in the not-too-distant future, WVU will have helped move the prevention of tick-borne diseases past precautions such as using insect repellent and checking for ticks on the body after spending time outdoors. And while the tick may remain tiny, it may no longer be so mighty.
