Proceedings of the 10th International Colloquium on Paratuberculosis

Public Health Keynote Lectures (Sunday Evening)
Paratuberculosis and Crohn’s Disease: Already Beyond Reasonable Doubt.
Tim Bull
St. George’s Hospital Medical School, London, UK
Crohn’s Disease (CD) is an important chronic disabilitating inflammatory disease that is increasing in
incidence. There is good scientific evidence that CD has both an underlying genetic susceptibility and an
infectious aetiology. That <strong>the</strong> infectious agent may be MAP has been a subject <strong>of</strong> much speculation, argument,
controversy and misinformation over <strong>the</strong> past decade. Despite detailed analysis, and partly because <strong>of</strong> <strong>the</strong>
complexities and technical difficulties in studying CD and MAP, <strong>the</strong> position has not been clarified fur<strong>the</strong>r than
suggestions <strong>of</strong> ‘a possible link’ or ‘insufficient and inconclusive scientific evidence’. This ambiguity has left
many clinicians sceptical and allowed a conservative and cautious attitude to persist. Of particular relevance
is that any successful resolution <strong>of</strong> this issue will not be without wide reaching consequences. A general
acceptance <strong>of</strong> MAP as a true zoonotic agent will have ramifications in many fields including domestic and wild
animal welfare, sustainable agriculture, economic planning <strong>of</strong> infection control policies, food and environmental
safety, clinical approaches to CD <strong>the</strong>rapy and possible legal complications. Thus any conclusions or truths
that can be derived from past or present studies should not be undertaken lightly, should be founded on good
scientific practice and devoid <strong>of</strong> conjecture.
A common perception has been that this is an insolvable dilemma, particularly since ethical restrictions
forbid human challenge studies. However, recent advances in technology combined with a more complete
understanding <strong>of</strong> immunological mechanisms in CD and mycobacterial mechanisms <strong>of</strong> pathogenesis have
enabled studies designed to confront this dogma. This presentation will summarise <strong>the</strong> crucial developments
and insights that are being revealed in this field including good scientific evidence for MAP presence, virulence,
infectivity, pathogenesis and response to treatment. It will show that consistent with <strong>the</strong> increased exposure
<strong>of</strong> humans to MAP from animals and <strong>the</strong> environment, MAP is present, unequivocally viable and persistent
in both normal human controls and with a significantly increased strength <strong>of</strong> association in CD patients.
It will show that persistence <strong>of</strong> MAP in humans, as in o<strong>the</strong>r pathogenic mycobacteria is associated with a
viable non-replicating intracellular phenotype and that MAP from humans are virulent in animals. It will show
that <strong>the</strong> degree <strong>of</strong> MAP infection and colonization in <strong>the</strong> human gut mucosa is patient specific but is able to
stimulate innate inflammatory responses predominant in CD. It will show that CD patients have MAP specific
immunological reactivities that are fully consistent with our knowledge <strong>of</strong> immune dysregulations underlying
inflammatory bowel disease. It will show that JD and CD have related genetic susceptibilities that are indicative
<strong>of</strong> defective resistance to mycobacteria and that <strong>the</strong>se defects can preferentially favour MAP pathogenesis.
It will additionally show that <strong>the</strong>rapy which includes anti-MAP activity can lead to improvement <strong>of</strong> CD. In
conclusion it will suggest that we now have more than enough good scientific evidence to show that MAP has
sufficient motive, means, opportunity and association with <strong>the</strong> scene <strong>of</strong> <strong>the</strong> crime to convince a jury to deliver a
verdict.
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