PULLMAN, Wash. – Washington State University professor William C. Davis and colleagues published a case report last month that provides more evidence that two gastrointestinal diseases, one in cattle the other in people, may be linked.

Davis is an immunologist in the Department of Veterinary Microbiology and Pathology in the WSU College of Veterinary Medicine. He explains that Johne’s disease, (pronounced YO-knees disease) is a major animal disease problem worldwide. It is caused by a microorganism known as Mycobacterium avium paratuberculosis, or MAP for short.

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Professor William C. Davis

MAP infections result in an inflammation of the lining of the bowel leading to severe damages in the gastrointestinal tract.  Once the process begins, the animal can no longer absorb required nutrients, develops severe diarrhea, loses weight, drops milk production, and eventually dies.

He also says humans can suffer a suspiciously similar disease known as Crohn’s disease that has been linked to MAP infections in some studies.  Estimates are that up to 1.4 million people in the U.S. suffer with Crohn’s disease, costing more than $1.7 billion in healthcare costs annually.

Here too, the intestine is inflamed resulting in severe diarrhea, excessive weight loss, debilitating abdominal pain, rectal bleeding, bowel obstruction, fistulas, and abscesses. About half of Crohn’s patients require surgery to remove a portion of their inflamed intestine.  Each day, about 55 people between the ages of 15 and 25 are diagnosed with Crohn’s disease in the U.S.

“MAP was initially theorized to cause Crohn’s disease in 1913 because of the similarities between the intestinal inflammation seen in cattle and humans,” explained Davis.  “It wasn’t until the mid-1980s when MAP was successfully isolated from three patients with Crohn’s disease that the idea gained more traction.”

Doubt quickly arose in the medical community as to whether MAP actually was the causative agent of Crohn’s. Investigators were unable to consistently demonstrate the presence of MAP in Crohn’s patients.  Other doctors isolated MAP alive and well in otherwise healthy subjects and some patients with other diseases.

Proponents in the MAP-causes-Crohn’s-disease camp counter by explaining that advances in technology have indeed revealed the presence of MAP in blood, tissues and feces in Crohn’s patients.  Still a lack of definitive proof has resulted in a continued reluctance to accept that MAP is a zoonotic pathogen, meaning it is one that causes disease in both animals and humans.

Ongoing studies in Davis’ laboratory in Pullman, Wash., and collaborative studies with investigators in India may now reveal why it has been so difficult to show MAP is the causative agent of Crohn’s disease, in at least some patients.

A survey of 42,400 subjects in India was recently undertaken.  The subjects had a variety of diseases, including subjects with the clinical features of Crohn’s disease and subjects with no apparent health problems. The survey found that humans, regardless of health status, are susceptible to MAP infection.

These findings are consistent with more limited studies in the US and elsewhere. What was overlooked is the similarity in the way Johne’s disease develops with the way another deadly disease, tuberculosis develops.

Tuberculosis is caused by a member of the same genus of bacteria as Johne’s disease. In the case of tuberculosis, the infection leads to an immune response by the body that controls the infection, but cannot eliminate the causative organism. Tuberculosis patients develop a lifelong latent infection and most do not develop the dreaded clinical disease.

The survey in India shows a latent infection also develops in humans following infection with MAP, identical to what occurs in cattle. Davis says studies thus far have only focused on demonstrating patients with Crohn’s disease are infected with MAP. “For these patients, the question has been, do they have Johne’s or Crohn’s disease?”

Last week, Davis and colleagues in the U.S. and India published a case report in Frontiers of Medicine http://journal.frontiersin.org/article/10.3389/fmed.2016.00049/full .  The report described a single patient, clearly infected with MAP, with the classic features of Johne’s disease in cattle, including the massive shedding of MAP in his feces. The patient was also ill with clinical features that were indistinguishable from the clinical features of Crohn’s. In this case though, a novel treatment approach cleared the patient’s infection.

The patient was treated with antibiotics known to be effective for tuberculosis, which then eliminated the clinical symptoms of Crohn’s disease, too.

“The findings presented in this case report suggest MAP is zoonotic and can cause disease in humans with the clinical manifestations of both Johne’s and Crohn’s disease, a key point that has been argued for more than 100 years now,” said Davis. “I suspected all along that it was only a matter of time before a patient would be identified that linked Crohn’s disease with an MAP infection.”

This case report adds more information to that reviewed recently by a group of gastroenterologists at Baylor University’s College of Medicine, who in their 2015 paper describe the evidence for and against the hypothesis that MAP infections cause Crohn’s disease.

Davis’ theory linking Crohn’s disease to MAP infections in humans, has driven him to devote a significant part of his career to the development of a vaccine to remove MAP from cattle, and thus from the food supply and the environment.

Regardless of whether or not MAP is causative, “We’re making significant progress on a vaccine,” explained Davis.  A cattle vaccine provides the greatest promise for controlling Johne’s disease and benefitting cattle, regardless of the uncertainty surrounding the associations to human Crohn’s disease.

 

Media contact:

Charlie Powell (509) 335-7073 (all hrs.) or cpowell@vetmed.wsu.edu