Lay Summary

Proposal No.  IBD-0107R2
Principal Investigator:  Balakrishnan S. Ramakrishna, M.D., Ph.D.
Applicant Organization:  Christian Medical College Vellore Association (India)
Project Title:  Is the increasing incidence of Crohn's disease in a low prevalence area associated with reduced exposure to infection with helminths?
Period of Award:  March 1, 2005 – February 28, 2007

Crohn's disease is characterized by uncontrolled intestinal inflammation.  This inflammation may partly result from a defect in the mechanism by which our intestinal immune system recognizes normally harmless bacteria that are present within the lumen of the intestine.  Parasitic worms such as hookworm and roundworm that live within the human intestine have developed mechanisms, primarily manipulation of immune responses within the intestine, to survive in the intestine for prolonged periods of time.  There is evidence to suggest that infection with these worms may condition the way in which the immune system responds to other antigens within the intestinal lumen.

Several scientists have noted that there is an inverse association between the degree of domestic hygiene and the occurrence of Crohn's disease.  The proposed study will examine the possibility that past or present infection with hookworms protects against the possibility of development of Crohn's disease in a susceptible population.  The study will be conducted in south India where diagnoses of Crohn's disease are increasing rapidly, while intestinal hookworm infestation is declining dramatically.

Exposure to hookworms will be detected using appropriate studies that will collect blood from subjects, separate the white blood cells, and then test them to see if they are activated on exposure to hookworm antigens.  These studies will be conducted on three groups of subjects - patients with Crohn's disease, patients with ulcerative colitis (a disease condition often linked with Crohn's disease in the grouping of inflammatory bowel disease), and healthy asymptomatic control subjects from a similar background.  Appropriate statistical analyses will then be carried out to detect associations between any of the study groups and the presence of lymphocyte activation by hookworm antigens.

There is as yet no direct evidence linking intestinal hookworm infestation (or the lack of it) with development of Crohn's disease.  We expect that the proposed study will detect such an association, if present.  If negative associations are found, this is likely to stimulate further research to identify molecules produced by these intestinal worms that have an ability to condition the mucosal immune system.  Potentially, this could lead to novel therapies for the management or prevention of Crohn's disease in susceptible populations.

The results of these studies should allow the detection of possible negative associations of Crohn's disease with hookworm infections.  This is a relatively unexplored area, and there is as yet no direct evidence of the hypothesis elaborated above.  If negative associations are found, this would direct future research to identify molecules in hookworm which are responsible for conditioning the mucosal immune system to prevent mucosal inflammation.  Potentially, this could lead to novel therapies for the management or prevention of Crohn's disease.