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This New Approach May Reduce The Spread Of Lyme Disease

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Finding an effective way to prevent the spread of tick-borne illness such as Lyme disease has been quite challenging over the past several decades.

Traditional approaches to reduce the possibility of tick bites have relied on physical barriers (screens on windows and doors), avoiding activities in at-risk environments (woods, long grasses), along with wearing long pants, long sleeves, socks and sturdy footwear. While insect repellents (i.e. DEET, picaridin, IR3535, oil of lemon eucalyptus [OLE]) are recommended by the CDC in adults, they should not be used in infants less than 2 months, with OLE not recommended under the age of 3 years, due to potential neurologic effects.

Other than reactive approaches—such as taking antibiotics after a suspected or confirmed tick bite—finding a way immobilize a tick after it attaches or begins to feed on a host may be one way to approach this complex and challenging problem.

One viable approach to control the tick population may be to focus on not only the tick's saliva, but the structure of the salary gland itself. Past research has shown that it's the saliva from a tick's bite which can transmit pathogens that lead to chronic and debilitating illnesses, such as Lyme disease, babesiosis, ehrlichiosis and anaplasmosis.

Now, researchers from Louisiana State University have developed a new approach that goes right to the place where a tick transmits disease: its salivary glands (which produce saliva).

Their approach is to harness the power of specific compounds known as ion channel blockers that can dry up a tick’s saliva by interfering with a delicate balance of ions in the salivary gland. This results in a drastic eduction in feeding time, which ultimately reduces the possibility of transmitting bacteria and other pathogens.

The research will be presented today at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition in San Diego.

"Lyme disease is exploding in the northeastern U.S.," said Daniel Swale, Ph.D., the project's principal investigator in a press release. "Most methods to kill ticks in the agricultural sector involve the use of neurotoxic insecticides, but it's difficult to effectively use these insecticides to control ticks in residential areas. So we wanted to identify a new way to control these disease-carrying ticks."

"We knew that the salivary gland is critical to the biological success of ticks, suggesting it had potential as a target for a pesticide that works through a new mechanism," said Zhilin Li, a doctoral student from Louisiana State University who is presenting the work at the meeting today.

Their approach was simple: if they can stop ticks from producing saliva in the first place, this would prevent them from feeding. So if they can’t feed, they would ultimately die.

The researchers chose to focus on a potassium ion channel—the Kir channel—because it plays a key role in the maintenance of salivary gland function and integrity in ticks (as well as mosquitoes), providing a way for potassium to move in and out of cells in the salivary gland. The movement of potassium in an out of such cells helps to maintain a specific chemical or ionic balance  that is integral to not only the secretion of saliva, but ultimately the survival of the tick itself.

To demonstrate this concept, the researchers fed ticks  cow’s blood laced with two compounds that interact with the Kir channels.

Results of the experiment demonstrated that 2 specific compounds, one known as VU0071063 and Pinacidil, a drug use to treat high blood pressure, were both effective in reducing secretion of saliva by at least 95%, translating to a 15-fold reduction in amount of ingested blood by the tick.  

The reduction in secretion of saliva and amount of ingested blood associated with administration of the compounds are important aspects of reducing the infectivity of ticks. Why? Because the ticks which fed on the cow’s blood laced with either of the compounds died within 12 hours. This window of time—12 hours—is  particularly relevant because transmission of bacteria and other pathogens via ticks' saliva into their human or animal hosts generally takes at least 12 hours and sometimes as much as 40 hours.

One caveat to the study: the experiments were conducted in artificial host feeding systems that contained a blood meal. This is still encouraging news, and future studies to use the compounds in a real life scenario, such as a rodent model, will test whether the treatment is effective in reducing transmission of pathogens and reducing tick survival.  

The researchers explained that the ticks removed from the blood meal before they died were already demonstrating concerning signs, including loss of neurologic and motor function with increased lethargy. 

Their explanation for the changes is related to an imbalance of sodium, potassium and chloride ions in the ticks. Typically during feeding, a tick recycles and returns excess water and ions from human or animal blood back into its host. However, the ticks exposed to the specific compounds were excreting more ions, while producing significantly less saliva, leading to a slow down and breakdown in metabolic and other life sustaining pathways. "We think their nervous system wasn't working normally, and we suspect that's why we saw high mortality in the treated ticks," explained Li.

It’s unclear at this time, but early results of this research indicate that the ion channel is found in the salivary gland only when the tick feeds, and then seems to vanish.  Further research to understand the types of cells within these specialized channels will be important to understand its ultimate function.

The hope is that it may be possible to develop a chemical spray or oral medication for not only animals, but people who live or work in high risk areas where Lyme disease and other tick-borne diseases is endemic.



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