Zoonotic Potential of Johne's disease
Association of M. paratuberculosis and Crohn's disease
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- Mycobacterium paratuberculosis has been implicated as a possible cause, or complicating
infection, in people with Crohn's disease. There is evidence both for and against this theory.
Examples of research findings that suggest an association between M. paratuberculosis and
Crohn's disease will be presented on this page. For a comprehensive review of this complex
subject, readers should obtain copies of two excellent reviews, one by R.J. Chiodini (1989), and
the other by D.E. Thompson (1994). These and other references are listed in the reference
section of this page. For general information on Crohn's disease, readers should visit the web
site sponsored by the U.S. National Institutes of Health and the Crohn's and Colitis Foundation of America (CCFA).
An extensive website dedicated to the theory that M. paratuberculosis does cause Crohn's disease was created by Mr. Alan Kennedy, an information technology consultant with Crohn's disease living in Ireland. This site presents one perspective on this controversial question. It is an excellent source of background information about Crohn's disease with several links to related websites. The website also provides full text access to recent publications on M. paratuberculosis and Crohn's disease.
- It is not the intention here to try and review the hundreds of scientific studies done in search of
the cause of Crohn's disease. Instead, I will present information about similarities between
Johne's disease in animals and Crohn's disease in humans, and studies that report direct and
indirect evidence of association of M. paratuberculosis with Crohn's disease.
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- Diarrhea, without blood, is a sign of Johne's disease in some animals but not others. In cattle,
diarrhea is a common early sign of M. paratuberculosis infection (cow with diarrhea, 235.4k). The diarrhea in cattle ranges from manure that is just more loose than normal,
to very watery manure. In ruminants that have pelleted feces, such as sheep, goats and deer,
diarrhea is less commonly seen. When these animals have Johne's disease, they continue
producing fecal pellets until the very late stages of M. paratuberculosis infection. Even then, fecal
consistency only becomes pasty and more like that of dogs or humans. Watery diarrhea in sheep
and goats due to Johne's disease is unusual. Diarrhea is also a common sign of Crohn's
disease. In Crohn's disease the diarrhea may be blood-tinged due to rectal bleeding. Bleeding
may be serious and persistent leading to anemia.
- Weight loss is a consistent sign of Johne's disease. The weight loss may be gradual or rapid.
In dairy cattle that develop signs of Johne's disease shortly after calving, the weight loss can be
extremely rapid due to the heavy demands on the physiology of cows producing 50 to 100
pounds of milk a day and the impaired intestinal function caused by the M. paratuberculosis
infection (Guernsey cow with marked weight loss, 276.9k). In other ruminants, the
weight loss is generally slower and may go undetected when the animals have a heavy coat of
hair or wool. Humans with Crohn's disease also suffer from weight loss. Children with Crohn's
disease may suffer delayed development and stunted growth.
- Abdominal pain, often in the lower right area, is a sign of Crohn's disease in humans and one that
is hard to measure in animals. It appears that cattle do not experience abdominal pain from
Johne's disease whereas goats do.
- Patients with Crohn's disease, in addition to diarrhea and abdominal pain, may have a variety of
symptoms not related to the intestinal tract such as arthritis, skin problems and inflammation of
the eyes or mouth. Extraintestinal signs of disease are not normally observed in Johne's disease.
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- Gross pathology is similar for Johne's disease in cattle and Crohn's disease. The site of
pathology is most often the ileum for both diseases. The ileum becomes very thick and the
mucosal surface has a corrugated or cobblestone appearance (thickened bovine ileum, 219.7k; thickened human ileum, 64k). In sheep and goats, thickening of the ileum
is not common. Lymph nodes adjacent to the ileum are enlarged in both Johne's disease and
Crohn's disease.
- Microscopic pathology is also similar in Johne's disease and Crohn's disease. In both diseases
the ileum is infiltrated with mononuclear inflammatory cells; macrophages and lymphocytes
(histopathology of a bovine ileum, 351.6k). Often macrophages fuse together to
form giant cells (giant cell in bovine ileum, 351.6k). Such an inflammatory response
is called granulomatous inflammation. It is similar in many ways to that found in tuberculosis,
however, the granulomatous inflammation found in Johne's disease and Crohn's disease is not
organized into well circumscribed granulomas or tubercles. Instead, granulomatous inflammation
in Johne's and Crohn's disease is diffuse. Caseation necrosis (dead cells that form a material
the color and consistency of thick cooked oatmeal) occurs in the center of lesions caused by
tuberculosis. Caseation necrosis is not generally seen in Crohn's disease or Johne's disease in
cattle. Johne's disease in deer and elk and sometimes sheep, however, may have caseation
necrosis of lymph nodes. A major difference between the microscopic pathology of Johne's and
Crohn's disease is that in Johne's, acid-fast bacteria (mycobacteria) are readily seen (acid-fast
stain of a section of bovine ileum, 351.6k), but in tissue from Crohn's patients, no
acid-fast bacteria are evident.
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- Risk factors for developing Johne's disease are related to the likelihood of exposure to M.
paratuberculosis. Thus, the infection status of an animal's mother and the herd in which the
animal is raised are the most important risk factors. Consumption of milk, water, or feed
contaminated with M. paratuberculosis is another risk factor for Johne's disease. It is important
to note that for most animal species there appears to be an age-dependent increase in resistance
to M. paratuberculosis infection. Hence, exposure to risk factors for infection are most critical
when animals are young and of much less consequence when animals become adults (see
epidemiology section of F.Y.I.).
- A variety of potential risk factors have been described for Crohn's disease, but no single risk
factor has been found to be critical. Thus, there is no known cause of Crohn's disease.
However, epidemiological evidence indicates that exposure of genetically susceptible individuals
to one or more factors in early childhood is important for development of Crohn's disease.
Among factors found to be statistically associated with Crohn's disease are:
- having a family member with Crohn's disease (in particular a mother),
- being breast fed a shorter time,
- being female, and
- living in an urban vs rural location.
- In summary, Johne's disease and Crohn's disease are epidemiologically similar. Both diseases
are chronic, progressive diseases of the ileum that are initiated in the early years of life. Johne's
disease is initiated by exposure to M. paratuberculosis. The factor responsible for initiation of
Crohn's disease is as yet unknown. No evidence either for or against exposure to animals with
Johne's disease, farm environments, or foods of animal origin, as being risk factors for development of
Crohn's disease has been published.
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- M. paratuberculosis is consistently isolated from cattle and goats with Johne's disease. Isolation
of M. paratuberculosis from sheep is much more difficult. Sheep strains of M. paratuberculosis
seem to have different nutritional requirements for in vitro growth than strains from other animals.
- M. paratuberculosis has been sporadically isolated from humans with Crohn's disease. In some
studies, cell wall-deficient forms of M. paratuberculosis, called spheroplasts, have been found.
Some investigators speculate that formation of spheroplasts is the reason why M. paratuberculosis can not be seen in acid-fast stained tissue sections from Crohn's patients and
why it is difficult to culture it from clinical specimens from Crohn's patients.
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- Virtually all animals with Johne's disease test positive for presence of a marker for the genome of M. paratuberculosis, called IS900. Occasional exceptions have been reported in deer with Johne's
disease where IS901-containing bacteria, closely related to M. paratuberculosis, have been found.
- Several recent reports (most listed below) have used this same IS900 "probe" to search for
evidence of M. paratuberculosis in humans with Crohn's disease. Study results and conclusions
vary considerably. Those that reported that no Crohn's patients test positive for M. paratuberculosis obviously conclude this bacterium has no significance to the disease.
Investigators who found that 40-72% of Crohn's patients test positive for M. paratuberculosis
suggest than it may be the cause of Crohn's disease, or at least a serious complicating infection.
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- Only a limited number of reports on treatment of animals for Johne's disease have been
published. In most all cases, therapy failed to cure the M. paratuberculosis infection.
- A small number of studies report attempts to treat Crohn's patients with drugs potentially capable
of eliminating M. paratuberculosis - drugs designed to treat tuberculosis. Results of those studies
vary considerably; some report cure or long-term remission of clinical signs of Crohn's disease,
others report no significant change in patient health. Studies that used clarithromycin have had
the greatest success.
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Crohn's disease tissue by southern blotting and DNA hybridisation with cloned mycobacterial
genomic DNA probes from a Crohn's disease isolated mycobacteria. Gut 29:1222-1228.
Caekenberghe, D.V. 1989. Crohn's disease, sulfasalazine, and mycobacteria. J.Lab.Clin.Med.
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Chiodini, R.J., H.J. Van Kruiningen, R.S. Merkal, W.R. Thayer Jr., and J.A. Coutu. 1984.
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Chiodini, R.J., H.J. Van Kruiningen, W.S. Thayer, and J.A. Coutu. 1986. The spheroplastic phase
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