Diagnosis and Control of Johne's Disease (2003) / Chapter Skim
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6. Johne's Disease and Crohn's Disease
6. Johne's Disease and Crohn's Disease
Pages 104-120
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From page 104... ...
This has been a controversial subject attracting strong adherents to both positions, but its resolution is essential for the development of rational approaches to disease management and prevention. Programs designed to limit human exposure to organisms from zoologic and other environmental sources will present enormous challenges if Map is found to be a significant human pathogen.
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From page 105... ...
Etiology of Crohn's Disease The cause or causes of Crohn's disease are unknown. Prominent hypotheses include an aberrant or autoimmune host inflammatory response to undefined antigens, infectious etiologies including Map, and aberrant immune response to a specific infectious agent.
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From page 106... ...
It has been suggested that there is a gradient of prevalence from northern Europe to Mediterranean countries (Eisen and Sandler, 1994; European Commission, 2000) and from northern to southern states in the U.S.
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From page 107... ...
IMPLICATIONS OF THE LINK Whether there are important human health implications associated with the development of a JD control program depends on the degree to which clinically significant human disease results from exposure to Map. It follows that the influence of an animal control program on human health will correspond to its capacity to meaningfully reduce exposure of susceptible persons to strains of Map that can cause disease.
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From page 108... ...
If the prevalence of human Map infection increases or is found to be greater than currently believed, independent consideration of JD control programs designed to limit human exposure could be warranted. Map and Crohn's Disease Important human health implications associated with the control of JD will be most strongly linked to determination of the effect of Map infection on the development of Crohn's disease.
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From page 109... ...
For example, if a subset of Crohn's patients from which Map could be isolated or identified responded to anti-Map therapy, while a similar subset from which Map could not be isolated or identified did not, a causal role for Map would be strongly supported for the first subset. The clinical understanding of Crohn's disease would be modified by such studies, and the door would open to developing new diagnostic and therapeutic tools for managing disease caused by Map, and to undertake focused studies of disease pathogenesis.
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From page 110... ...
Provision of adequate resources to gain this information should be a priority. There is insufficient knowledge to determine whether reduction of disease caused by Map should be addressed through treatment of persons already infected, through epidemiologic control programs designed to prevent human exposure, or to a combination of those approaches.
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From page 111... ...
Chronic diarrhea, dull hair, weight loss, decrease in lactation Chronic a Blood in stool Rare Rare Vomiting Rare No Abdominalpain Yes Unknown Obstruction Yes Extraintestinal manifestations Polyarthritis Yes, but rare Uveitis Yes, but rare Skin lesions Amyloidosis Hepatic granulomatosis Renal involvement Clinical course Remission and relapse Yes Yes, but rare Yes, but rare Yes, but rare Yes No No No No yesb Yes yesC Yes aNot seen in sheep bGoats primarily CGoats, deer, primates primarily, also camelids SOURCE: Adapted from European Commission (2000)
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From page 112... ...
Occasionally Caseation No Usually note Fissures Yes No Visible acid fast bacilli No Yese aIleum and jejunum are the initial and most frequent locations bNot always in sheep Predominant feature in lymphocytic-paucimicrobial form Varies with species eScarce or absent in lymphocytic-paucimicrobial form SOURCE: Adapted from European Commission (2000) The data obtained from human studies directed at the cause of Crohn's disease are varied and conflicting: .
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From page 113... ...
Hybridization studies of Crohn's tissues in situ using probes directed against IS900 (Hulten et al., 2000b, 2001) Treatment of Crohn's patients with anti-mycobacterial therapy (Table 6-3)
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From page 114... ...
Studies of human disease tend to be small and highly selected, and studies of the effectiveness of antimycobacterial chemotherapy in Crohn's disease have frequently been uncontrolled and not based upon in vitro antimicrobial sensitivity. The finding of Map in Crohn's tissues by culture, PCR, in situ hybridization, or other methods may reflect several possibilities (an innocent bystander has merely colonized the intestine; a secondary infection that is not the cause of Crohn's disease; a surrogate marker for another agent that has not been detected; a false positive result especially in the case of PCR; an actual cause of Crohn's disease)
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From page 115... ...
The lack of uniform results in pathogen isolation studies, serologic response, or responses to antimycobacterial therapy could derive, in part, from the possibility that only a subgroup is related to Map. Evidence Required to Support a Cause-and-Effect Relationship What evidence would establish Map as a human pathogen and as a cause of Crohn's disease?
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From page 116... ...
Many parasitic illnesses and viral diseases have unique hostdependent clinical manifestations, such that animal models imperfectly reflect human clinical disease syndromes. The most notorious recent example of this was the claim that HIV did not cause AIDS because the third postulate was not fulfilled in that human viruses do not reproduce the disease in animal models (Duesberg et al., 1989~.
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From page 117... ...
· Data insufficient No studies specifically evaluate the exposure of patients with CD to Map. Detailed surveys of potential environmental sources of Map would be required to conduct these studies and this information is not available.
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From page 118... ...
Moderate evidence of causation: A higher incidence of Crohn's disease among susceptible people who consume products containing or contaminated with Map. Conditions conferring host susceptibility are not well understood.
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From page 119... ...
Because it is unlikely that all of these studies will be done, two lines of evidence would provide strong evidence to support a role for Map in the causation of Crohn's disease. Briefly stated, the regular isolation or identification of Map or of Map RNA-DNA from Crohn's disease tissues and not from appropriate control groups, with the unequivocal therapeutic response of patients with Crohn's disease to therapy directed at Map, would strongly implicate Map as a human pathogen and as a cause of Crohn's disease.
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From page 120... ...
120 DIAGNOSIS AND CONTROL OF JOHNE'S DISEASE There is insufficient evidence to prove or disprove that Map is a cause of Crohn's disease. The problem is of such importance and the hypothesis sufficiently plausible to warrant increased research to resolve the questions.
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