Insight: Research Edition

Fall 2005

Rural Disease Makes Jump to Select Agent

When Dr. John Belisle was in junior high school, he remembers going hunting with his cousins in Nebraska. After they killed and skinned a rabbit, the reaction from his grandmother, whose parents had emigrated from Russia, was anger and fear. She associated rabbits with tularemia, a disease more commonly feared in her parents’ home country. She yelled at the boys and made them scrub down. Tularemia, also known as rabbit fever, can be fatal.

Dr. Belisle didn’t think too much more about tularemia over the course of his education and ensuing career in the biomedical sciences, but today tularemia is very much on his mind. As a faculty affiliate with the Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Diseases research and training, Dr. Belisle has undertaken a research project that he hopes will one day lead to an effective vaccine against tularemia.

“Tularemia is a disease most often associated with rural areas and hunting,” said Dr. Belisle, who is a Professor in the Department of Microbiology, Immunology and Pathology. “People become infected through the bite of infected insects or by handling sick or dead animals. Hunters usually get the disease from fleas found on rabbits or other small rodents.”

According to the Centers for Disease Control and Prevention (CDC), about 200 human cases of tularemia are reported each year in the United States. Symptoms are similar to the flu and include fever, chills, headache, respiratory problems, joint pain and dry cough. Skin ulcers also can develop if the source of infection is a bite, rather than inhalation. Tularemia can be treated with antibiotics when diagnosed properly.

“The reason we are concerned about tularemia is because of its potential for use as a bioweapon,” said Dr. Belisle. “The bacterium that causes tularemia, Francisella tularensis, is highly virulent – only a few organisms can cause infection – and it can be very acute. Also, the precedent has already been set. The disease was weaponized by the Soviet Union during the Cold War. If tularemia were used as a bioweapon today, the bacteria would likely be aerosolized and could potentially infect large numbers of people. People who inhaled the bacteria could develop severe respiratory illness and our health care system would be rapidly overwhelmed.”

Dr. Belisle noted that Francisella tularensis, while not a mycobacterium, shares several traits with the bacterium that causes tuberculosis, which is the primary research focus of his laboratory. The bacterium is intracellular and lives in the host’s macrophages.

“We hope that by applying the methodologies and approaches we’ve developed with Mycobacterium tuberculosis, we will be able to move quickly in our studies of Francisella tularensis,” said Dr. Belisle. “Our goal is to develop vaccine candidates ready for clinical trials in four years.”

The research team will first look at various subcellular fractions of the bacterium that are able to induce a protective T-cell response in the host. They will then look at specific proteins within the fractions, and then at individual proteins that induce a protective response. After identifying several candidates, these will be formulated into clinical vaccines and used in clinical trials. Dr. Belisle said the greatest challenge for the team, because of the bacteria’s highly virulent nature, will be developing good models that show a protective response. On the plus side, because the bacterium grows much faster than the tuberculosis bacterium, studies should be able to, theoretically, progress much more quickly.

“We also are adding additional personnel to assist in this project and, of course, we already have great expertise available to us here on campus, “ said Dr. Belisle. “A great thing about CSU and the College is the ability to find highly qualified collaborators. We are working with two immunologists, Drs. Steve Dow and Catherine Bosio, who will help us with their expertise in animal models and evaluation of immune response.”

Dr. Dow is an Associate Professor in Clinical Sciences and Dr. Bosio is an Assistant Professor in the Department of Microbiology, Immunology and Pathology. Dr. Belisle’s team also is working closely with Dr. Jeannine Peterson at the CDC’s Division of Vector-Borne Infectious Diseases in Fort Collins.

Dr. Belisle and his cousins didn’t contract rabbit fever those many years ago in Nebraska – he doubts the rabbit was infected. But, for his grandmother, old fears take a long time to die. And, in today’s new world of biodefense, bioweapons and bioterrorism, old fears have taken on a new life. This time though, scientists are hoping their research will lead to a better preventive approach to rabbit fever that will take away the potential threat of a weaponized tularemia bacterium.