TRICHURIS SUIS THERAPY FOR ACTIVE ULCERATIVE COLITIS: A RANDOMIZED CONTROLLED TRIAL

Authors: SUMMERS, ROBERT - UNIV OF IOWA, IA; ELLIOTT, DAVID - " "; Urban, Joseph; WEINSTOCK, JOEL - " "

Submitted to: Gastroenterology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2004
Publication Date: 4/1/2005
Citation: Summers, R.W., Elliott, D.E., Urban, J.F. Jr., Thompson, R.A., Weinstock, J.V. 2005. Trichuris suis therapy for active ulcerative colitis: A randomized controlled trial. Gastroenterology. 128:825-832.

Interpretive Summary: Mouse models of inflammatory bowel disease (IBD) have shown that infection with worms can prevent or ameliorate colitis. These models were designed to test the hypothesis that humans from industrialized Western countries with few worm infections express an immune dysregulation that results in increased expression of IBD that is not observed in lesser developed countries where worm infection is common. Pigs and man share many infectious agents because of similar immune and physiological systems and because of agricultural practices that have brought them in proximity. Trichuris is a genera of whipworms that infect many different mammals but are species specific in their ability to develop into a complete infection. Man has been reported to be infected with the pig whipworm, but not to develop a complete infection. The pig whipworm, Trichuris suis, appears to be asymptomatic in man and represents a naturally attenuated infection that cannot reproduce. This provided an opportunity to test the hypothesis that exposure to a worm would reduce the severity of IBD. A double-blind and placebo-controlled study was conducted at the University of Iowa. There was a significant improvement in IBD disease index in individuals refractory to other conventional forms of treatment that were fed T. suis eggs compared to placebo controls. This observation supports the hypothesis that immunological dysfunction may result from insufficient exposure to certain infections that stimulate a balanced immune response. These results can be expected to impact the study of several other immunologically based diseases and the search for natural products that can substitute for worms in induction of a protective response.

Technical Abstract: Background: Ulcerative colitis (UC) is most common in Western industrialized countries where helminths are rare. Inflammatory bowel diseases are uncommon in developing countries where helminths are frequent. People naturally colonized with helminths exhibit altered immunological responses to various antigens. In experimental animal models, helminthic colonization can prevent or improve colitis in part due to induction of regulatory T cells and cytokines. After observing encouraging responses in patients with active UC who received the helminth Trichuris suis open-label, we embarked on a double-blind placebo-controlled clinical trial of T. suis ova in the therapy of active UC. Methods: The study was a 12-week double-blind, placebo-controlled trial. Fifty-four patients with active UC, defined by an UC Disease Activity Index of =4, received suspensions of 2,500 T. suis ova or placebo given at 2-week intervals. The primary efficacy variable was improvement of at least 4 points on the Disease Activity Index. Results: After 12 weeks of T. suis ova therapy, 13 of 30 patients improved (43.3%) compared with 4 of 24 patients given placebo (16.7%), P = 0.04. Respondents showed progressive improvement beginning week 4 of treatment. There were no side-effects or complications attributable to the therapy. Conclusions: In patients with active UC, T. suis ova-therapy was safe and more effective than placebo. This finding also supports the premise that natural exposure to helminths like T. suis affords protection from immunological diseases like UC.