Therapeutic Colonization With Trichuris suis

To the Editor.—In the May 2006 issue, Kradin et al1 described the histology of live helminths and mucosa from a boy with highly refractory Crohn disease treated with Trichuris suis ova. Previous treatment with corticosteroids, cyclosporine, infliximab, methotrexate, thalidomide, azathioprine, and adalimumab had failed. A posttherapy computerized tomographic scan showed thickened terminal ileum and distal colon, and colonoscopy revealed diffuse colonic disease of variable severity, a rectal ulcer, a tight stricture at 25 cm, and a worm in the cecal region.We would like to address several issues the authors raised.1. It is highly unlikely that T suis causes prolonged colonization of humans. In our studies of T suis ova therapy in ulcerative colitis and Crohn disease, we performed colonoscopy in some patients and occasionally saw helminths of variable size and maturity.2–4 Ova in the stool were never detected despite regular examinations, suggesting that the worms never reached maturity. In patients who had been off ova therapy for several months, including some patients who were taking various immunosuppressants, we never saw eggs in the stool or parasitic forms on colonoscopy. Also, farmers who are frequently exposed to T suis by close contact with colonized pigs never develop clinically associated disease or chronic T suis colonization. Thus, the authors' suggestion that prolonged parasitic colonization may be a concern is speculation.2. The authors observed chronic inflammation in the mucosa that did not appear directed toward the helminths. It more likely was caused by active Crohn disease. In our cases, there was no increase in mucosal inflammatory cells, eosinophils, or histiocytes in the vicinity of worms. This is the typical host response to this helminth.3. Helminths likely induce various immune modulatory effects. The authors noted a marked predominance of CD4+, CD20+, and small numbers of CD8+ lymphocytes. It is known that helminths induce eosinophilia and TH2 cytokines, and the authors have provided evidence supporting this concept. However, it is unlikely that helminths simply alter the TH1-TH2 balance. Recent studies indicate that helminths stimulate the development of regulatory T cells that reduce both TH1 and TH2 responsiveness.5–84. The authors cited an article that reported a case of severe colitis caused by Campylobacter jejuni in a patient with trichuriasis.9 Campylobacter jejuni alone causes a severe life-threatening colitis10 and it is highly speculative whether coinfection with Trichuris accentuates such infections. Although the abstract of the article reported T suis ova in the stool, the actual text stated that “microscopy showed Trichuris trichiura larvae”. Trichuris larvae are not normally seen in stool specimens, no adult forms were seen on colonoscopy, and improvement occurred prior to treatment with mebendazole. If this Somolian immigrant was colonized, it was almost certainly the result of a helminth other than T suis. We suspect this was an error that the authors failed to address.5. As is often the case with far-advanced disease, none of the recognized therapies was effective, apparently including 5 oral doses of T suis ova. We suspect this patient had irreversibly altered intestinal function.