What Makes Ticks Tick?

Thursday, February 18, 2010

Band of OSU researchers work to understand these tiny creatures and the big-time diseases they transmit

Since the 1960s, Oklahoma State University has been known for excellence in research on ticks and tick-borne diseases.  Though many members from the original group have changed, OSU still maintains a leading tick research program.  OSU’s multidisciplinary unit of more than 16 researchers represents the Division of Agricultural Sciences and Natural Resources, the Center for Veterinary Health Sciences and the College of Arts and Sciences.  Currently, the group has 17 externally funded tick research projects underway, totaling more than $2.7 million.

With studies ranging from tick ecology and emerging infectious diseases to the development of vaccines for the control of ticks and tick-borne pathogens, the group’s work is especially relevant for Oklahoma, a state known for large tick populations and numerous yearly cases of Rocky Mountain spotted fever, tularemia and other tick-transmitted diseases.  As tick species have spread to new regions of the country over the last 20 years, their work is valuable to the nation as well.

“Our tick research program is one-of-a-kind,” said Dr. Stephen McKeever, OSU’s vice president for research and technology transfer.  “The collection of talented faculty paired with unique facilities and equipment make our program a resource to the state, nation and world.”

Dr. Katherine Kocan, Regents Professor and Sitlington Endowed Chair of Food Animal Research at CVHS, has worked with OSU’s tick research group for 35 years.  “Ticks have worldwide impact on both animal and human health, but Oklahoma is particularly plagued by ticks,” Kocan said.  “The tick problem impacts humans, wildlife, companion animals and cattle.  The people in our overall group are working on most all aspects of ticks and tick-borne pathogens.”

Ticks are the most common transmitters of vector-borne diseases in the U.S.  They pick up pathogens in one of their three life stages.  Larvae, which hatch from eggs and immediately begin seeking hosts, usually feed on small mammals like rodents.  After successfully feeding, the larvae fall off and molt into nymphs, which feed on small vertebrates.  Finally as adults, ticks feed on larger mammals, such as dogs, cats, deer, cattle and humans.

“Ticks are very complicated creatures,” Kocan said.  “In order to transmit pathogens, they need hosts serving as reservoirs of pathogens to become infected and then they need to feed on susceptible hosts to transmit the pathogens.  Ticks don’t have many natural enemies.”

Kocan and research scientists José de la Fuente and Ed Blouin work as a team to develop vaccines for ticks, which unlike chemical control, are a true solution for tick problems, Kocan says.  The team is currently working on a dual-target vaccine for cattle that will control tick infestations as well as reduce the vector capability of ticks so they don’t become so highly infected with pathogens.  The target of the vaccine is anaplasmosis, currently the only tick-borne disease of cattle in the U.S.  Kocan says tick infestations alone have a major economic impact on cattle production in Oklahoma.

Kocan and those working in her lab over the past several years have already made extraordinary progress in understanding anaplasmosis.  She and her team were the first to determine the pathogen’s developmental cycle in ticks.  They also created cell culture lines for the pathogen – a system that has lead to the ability to do research on a variety of tick-borne pathogens worldwide.  Cell culture lines are a huge resource for researchers, Kocan says, because they allow for research on pathogens without the use of animals.

Oh Deer

OSU researchers are also examining the anatomy of the tick itself.  Dr. Debbie Jaworski, assistant professor, and Dr. Jack Dillwith, professor, from the department of entomology and plant pathology in the Division of Agricultural Sciences and Natural Resources, are exploring ticks on a molecular level to determine which tick genes may be involved in tick feeding and disease transmission.   Dillwith has been studying the components of tick saliva that allow ticks to feed on a host for several decades. One of Jaworski’s current projects is the development of a model for the transmission of pathogens from ticks to deer.

Experts agree that the estimated 20 million deer residing in the U.S. drive tick populations.  Deer are the primary host for two major tick species, Ixodes scapularis, the black legged tick, and Amblyomma americanum, the lone star tick.  Previously considered an insignificant vector of disease, the lone star tick is now a major vector of disease-causing pathogens, which instigate an array of dangerous health conditions in humans and animals.

With her model, Jaworski is attempting to determine how the lone star tick transmits the pathogen Ehrlichia chaffeensis to deer.  Although the pathogen is not harmful to deer, it causes major health problems and even death when transmitted to humans, through a disease known as human monocytic ehrlichiosis.

“White tail deer are natural reservoirs for Ehrlichia chaffeensis,” Jaworski said.  “It’s likely that lone star ticks feed primarily on deer because we have such high deer populations.  The problem arises when the ticks carrying the pathogen feed on hosts other than deer, such as humans.”

Jaworski is looking for the bacteria located in ticks, how the bacteria are activated once the tick starts feeding, and what makes the bacteria move to the tick’s salivary glands, the site of transmission.

“Human monocytic ehrlichiosis is an emerging infectious disease,” Jaworski said.  “By understanding how the tick responds to the pathogen we can determine how to prevent it from spreading.”

Studying the spread of disease

Dr. Susan Little, professor and Krull-Ewing Endowed Chair of Veterinary Parasitology at CVHS, also studies ehrlichiosis, among several other tick-transmitted diseases.  As head of the Krull-Ewing Laboratory for the Study of the Ecology of Tick-borne Diseases, Little’s group focuses on tick-borne diseases shared by people and animals.

“Wildlife serve as reservoir hosts for many tick-borne pathogens, including the agents of ehrlichiosis, the most common tick-borne disease of people in the southern U.S., and Borrelia burgdorferi, the cause of Lyme borreliosis,” Little said.  “Both dogs and people can develop disease following infection with these agents.”

Using dogs as a sentinel species, Little tracks where these infections occur nationally and looks at the risk for infection in people by measuring the prevalence of infection in dogs.  She works to understand the factors in nature that conspire to create the risk of infection, such as how long a tick must feed to cause infection in a dog, and the ways ticks behave in nature and on animals as it relates to disease transmission.

In addition, Little works to identify novel tick-borne disease agents being transmitted to people and dogs.  She is currently examining Southern Tick Associated Rash Illness (STARI).  Seen since the 1980s in patients from the southeastern and south central U.S. who have been bitten by a lone star tick, STARI is “a real conundrum for the health community,” Little says.  Those infected experience the hallmark target lesion common to Lyme disease along with mild flu-like symptoms.  However, they do not test positive for Lyme.

Little’s lab was the first to successfully culture the organism thought to cause the disease.  Their work provided a much needed source of organisms for the development of diagnostic assays and formed a basis for future studies investigating the role of the organism as a human disease agent.

Ecological Impacts

Dr. Kristen Baum, an assistant zoology professor in the College of Arts and Sciences, also studies tick ecology.  She and Dr. Mason Reichard, an assistant veterinary pathobiology professor at CVHS, recently completed a project that, in part, examined landscape features common to cases of Cytauxzoon felis, a tick-borne pathogen typically fatal for domestic cats.

Researchers at OSU in the 1980s showed that bobcats are the natural reservoirs for the pathogen, which causes a condition in domestic cats known as “bobcat fever.”  The disease is quite common in domestic cats in Stillwater, and Baum and Reichard were able to access ten to twelve years of records from OSU’s Boren Veterinary Medical Teaching Hospital and Oklahoma Animal Disease Diagnostic Laboratory on cats infected with the pathogen.

Through the study, Baum confirmed the ticks carrying the disease were located in natural areas where different habitats come together, such as a well-wooded residential area.  Reichard discovered a consistent seasonal occurrence of the condition in May and early October.

The study also implicated the lone star tick in the transmission of Cytauxzoon felis.  Reichard said the American dog tick had previously been the only tick species associated with the transmission of the pathogen.

“For more than 20 years the American dog tick was thought to be the only vector for Cytauxzoon felis in the U.S.,” Reichard said.  “Our study demonstrated the emergence of the lone star tick as a new vector.”

Armed with these findings, Reichard is continuing the work and hopes to develop a strategy to control the spread of bobcat fever.  In the long term, he would also like to work toward a treatment for cats.

Despite all these results and accomplishments, the researchers say they have only touched the tip of iceberg with research on ticks and tick-borne pathogens, and they want to do more.  With plans for continued progress that builds on a 50-year legacy of excellence, the group is creating a core tick research facility and has established themselves as the National Tick Research & Educational Resource.

Although the endeavor will require additional funding, Kocan believes OSU’s tick research program is equipped and prepared to go to an even higher level.

“OSU has a unique opportunity to continue its tradition and enhance its prestige as a university of excellence worldwide for tick research,” Kocan said.  “With the relevance of tick research to real-world problems, the recognition and research support we have from federal agencies and industry, and our location right in the middle of tick country, we are poised to continue to be a leader in research on ticks and tick-borne pathogens.”