Is Crohn's Disease linked to Johne's Disease? (Proceedings)

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Is Crohn's Disease linked to Johne's Disease? (Proceedings)

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Oct 01, 2008

This question can stimulate some very lively discussions. Understandably, many livestock producers can respond very negatively to the topic. Given that many producers already feel challenged by questions about perceived negative impacts of modern production methods, ranging from food safety, to the environment, to animal welfare, the possibility that humans may be threatened by an animal disease present in their herd is not a happy prospect.

This question is a very important one for numerous reasons. In fact, the answer to this question is a critical determinant of how we should respond to the occurrence of JD in cattle herds. If it is determined that the causative agent can transfer from cattle to humans and cause Crohn's disease, then this problem warrants very serious attention in order to protect human health. On the other hand, if it does not appear that the agent harms humans, then the primary concern about this disease is its debilitating effect on cattle and resultant economic losses to the herd. Therefore, resolving and agreeing on the answer to this question should be a high priority.

Unfortunately the answer to this question is not yet clear, and it is very unlikely that an unequivocal answer can be provided in any short time frame. It is worth looking at why this is the case.

Although there are simple infectious diseases that fulfill Koch's postulates, such as polio or smallpox, where infection with the pathogen equates with disease occurrence, many infectious diseases are more complicated. In such cases, occurrence of disease requires more than just the invasion of the pathogen, and sometimes the pathogen can be present without disease occurrence. Crohn's disease is a multifactorial problem that appears to have a complex etiology. Several genetic factors have been associated with the disease, but it appears these provide predisposition to the disease and some other inciting factors must be present for disease to occur.

When Crohn's disease was first characterized, an infectious etiology was suspected, and MAP seemed a likely candidate because the disease closely mimicked Johne's disease in ruminants. No pathogen was identified using the methods available at the time, and as understanding of the immune and inflammatory systems advanced, the disease was seen as an example of inappropriate inflammatory response without known etiology. Thus it has been categorized as inflammatory bowel disease without specific cause, and anti-inflammatory agents have been a mainstay of therapy. Continued technological developments of gene probes as diagnostic tools that allow organism identification without culture prompted reexamination of the cause of Crohn's. Recent studies have pursued microbiological detection. Numerous studies have found evidence of MAP infection in CD patients, although others have failed to identify this agent. Looking at a substantial number of studies it is common to find that more CD patients than control subjects have the pathogen, associating the agent with the disease. It is reasonable to hypothesize that MAP infection stimulates an exuberant inflammatory response in people with predisposition to the disease, but also possible that the pathogen is a secondary rather than primary agent of disease. Numerous epidemiologic studies of CD implicate an environmental component of the disease, and presence of MAP would fit such a role.

Unfortunately, to date no consensus has been reached by medical specialists on the specific causal features of the problem. Because the disease is chronic and insidious and causes substantial suffering in affected individuals, and because large and increasing numbers of people are affected by the disease, clarifying the etiology has become a subject of increasing study. It is fair to say that many studies now point to infection as a component of the disease. Specifically, numerous studies show MAP present more frequently in patients than controls, evidence of immune response to MAP in affected people, association of MAP with lesions, evidence of MAP infection preceding CD occurrence, and positive response with remission of signs in patients treated with antibiotics targeting MAP. On the other hand, some studies refute these findings, and several other infectious agents have also been implicated as possibly associated with the disease. There appears to be reluctance by the medical community to make definitive statements about the cause of CD at present.

Furthermore, even if consensus is reached that MAP infection is involved in development of CD that leaves the question of where the infection is contracted. Although MAP is a thermally resistant organism and some organisms can survive standard pasteurization methods, it is not a forgone conclusion that MAP exposure occurs primarily via milk, as some people infer. Even if infection with MAP is part of the problem, there are numerous routes of possible exposure, including other CD patients, water sources, meat and milk. There is currently no information to indicate what an infectious dose might be, or what routes of exposure might present this dose. So even if the medical community implicates MAP infection, there remain needs to evaluate possible preventive practices to avoid infection.

How should the veterinary community and livestock producers respond to the possibility that MAP causes CD? It has been established over the last decade that our US dairy industry has a high herd prevalence of JD infection. While many herds have low infection rates, some are much higher. For now there is no definitive answer to whether JD infection in cattle makes the occurrence of CD in humans more likely (i.e. Is Crohn's disease linked to Johne's disease?). Mounting evidence says that the answer to this question may well be "yes". Disregarding this reasonable possibility, or just waiting to see what is decided seem like poor choices. Working to decrease prevalence of this infection in cattle seems like the wisest course. Since high prevalence of JD is detrimental to the herd, and since low prevalence of infection gradually becomes higher if left unchecked, efforts to decrease prevalence are warranted anyway.