Tackling Disease from the Inside Out

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Linda Mansfield is working to prevent enteric disease in swine and cattle. (view larger image)

Diarrhea.  Almost everyone gets it at some time, and almost no one wants to talk about it.   

It may not make for polite conversion, but diarrheal illness is a serious health problem in the United States and the world.  “Bad” food is often the culprit.  Each year, food-borne pathogens cause an estimated 76 million illnesses, 325,000 hospitalizations and 5,000 deaths in the United States alone, according to U.S. Department of Agriculture Economics Research Service data.

To help address this serious problem, MSU AgBioResearch large animal clinical scientist Linda Mansfield is part of a multi-institutional effort involving more than 30 scientists at nine universities that is working to improve food safety by preventing and controlling enteric (intestinal) diseases in swine and cattle. 

“You can improve food safety by intervening at several critical points,” Mansfield said. “There’s been a lot of emphasis on postharvest food safety, but eliminating or reducing the pathogen threat before products leave the farm improves safety even further.  To do that, you need to know your enemy.”

Campylobacter jejuni, one of the most prevalent bacteria that cause gastrointestinal disease in the United States, is one of several pathogens that Mansfield and her collaborators are investigating.  It is carried by poultry, cattle and swine, and it can be transmitted to people through meat and milk.  The illness it produces is distinctly unpleasant – vomiting and diarrhea that can progress to bloody diarrhea that lasts for seven to 10 days.  Infection withCampylobacter jejuni has also been linked to cancer of the digestive tract and to development of autoimmune diseases such as Guillain-Barré syndrome, Miller Fisher syndrome and reactive arthritis.  People can die from these autoimmune diseases or be left with lameness or paralysis.

“Right now, little is known about how Campylobacter causes disease in humans and animals, and there are few genetic tools for these studies,” Mansfield said.  “Thus, it has been difficult to develop vaccines for people or animals.  And it’s tricky.  For example, if you don’t know how Campylobacter causes autoimmune disease, a vaccine may actually induce it.”

Mansfield’s Comparative Enteric Diseases Laboratory at MSU has developed a mouse model that is being used to study the genetics of C. jejuni

“These mice act as surrogate human patients to help us understand how this bacterium causes disease,” she explained.  “We’re also using them to test treatments and vaccines to prevent Campylobacter infections.  Screening a large panel of C. jejuni strains in these mice has allowed us to recognize that the genetic makeup of the bacterium—and of the human or animal—determines whether the outcome is mild or severe diarrheal disease.  We have also used these mice to show that particular strains of C. jejuni cause autoimmune disease and others do not.  Collectively, this research will allow us to decide which strains are important to control.”

Mansfield and her fellow researchers classified the strains into categories, called pathotypes, on the basis of the disease they cause. Working with Michael Konkel at Washington State University and Gireesh Rajashekara at Ohio State University, she is identifying the C. jejuni virulence factors that are most important in producing severe diseases in humans.

“The ultimate goal is to rid food animals of this bacterium to prevent further transfer to people,” she said.      

C. jejuni is just one of the pathogens being investigated by the research group. Together, the researchers aim to significantly improve the detection of novel or emerging causes of enteric diseases; develop interventions and preventive measures that reduce the incidence of enteric infections of cattle and swine; and provide training and dissemination of information to students, producers, veterinarians and diagnostic laboratories. 

“We are among the few people who actually like talking about diarrhea,” Mansfield said.  “And it’s important that we don’t talk just to ourselves.  The more we know about these pathogens – especially the ones that are the real menace – the more misery we can help prevent.”

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