Crohn’s Disease Studies
UPDATING THE SCIENCE OF THE MAP IN CROHN’S DISEASE CONTROVERSY – A CALL TO ACTION
Sean M. Karp, MD1, *Timothy R. Koch, MD1, Gerald Pang, PhD2
1Section of Gastroenterology, Washington Hospital Center, Georgetown University School of Medicine, Washington, DC, USA, 2Discipline of Immunology and Microbiology, University of Newcastle, Newcastle, New South Wales, Australia
Background: The December 14, 1998 NIH/NIAID workshop: “Crohn’s Disease – Is there a microbial etiology? Recommendations for a research agenda” was organized to review evidence for and against the hypothesis that the bacterium Mycobacterium avium subspecies paratuberculosis (MAP) is the cause of Crohn’s disease (CD). The workshop conclusions stated that there is insufficient evidence to prove or disprove that MAP is a human pathogen or that it is the cause of CD. It recommended further research into the etiology and pathogenesis of MAP in CD through an extensive list of research requirements designed to contribute sufficient knowledge and data so that a firm conclusion could then be achieved. The workshop stressed the need to define a potential infectious etiology, to characterize the host immune and inflammatory responses, and to conduct crucial epidemiological and familial genetic research. Despite the absence of an assigned champion to follow up and ensure that this work was completed, additional basic and clinical research has been reported by multiple centers around the world, contributing to our body of knowledge regarding MAP in CD.
Aim: The aim of this study was to evaluate new knowledge and data involving MAP in CD. A detailed examination was made of all publications identified in a literature search.
Results: Over 145 clinical and laboratory studies demonstrate evidence supporting an association between MAP and CD. Eleven detection studies indicate that up to 95% of all CD patients are infected with MAP. Due to improved methods involving PCR and DNA hybridization techniques, the majority of recent studies have shown a significantly higher frequency of MAPin CD compared to older studies. Higher rates of seroreactivity against MAP antigens were detected in CD patients compared to controls. Six clinical trials using MAP specific drugs have shown a mean remission rate of 52% (range: 44%-89%). More knowledge has accumulated regarding drug selection and enhanced clinical efficacy. In all, over 145 studies have been published that respond to the needs identified by the 1998 workshop.
Conclusion: Significant basic and clinical research has been conducted in the evaluation of an association between MAP and CD. The results supports our belief that for the future of causative research in CD, it is imperative to convene experts for a formal conference to update the 1998 workshop and to establish new clinical and research directions for this important aspect of Crohn’s disease.