title: Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial.
abstract: Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3(rd) dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤ 14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation.
  
  
  BACKGROUND
  University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. pbg@ssi.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Bager
authors.forename: Christian
authors.initials: C
authors.lastname: Kapel
authors.forename: Allan
authors.initials: A
authors.lastname: Roepstorff
authors.forename: Stig
authors.initials: S
authors.lastname: Thamsborg
authors.forename: John
authors.initials: J
authors.lastname: Arnved
authors.forename: Steen
authors.initials: S
authors.lastname: Rønborg
authors.forename: Bjarne
authors.initials: B
authors.lastname: Kristensen
authors.forename: Lars K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: Jan
authors.initials: J
authors.lastname: Wohlfahrt
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
mesh_terms: D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D041981:Gastrointestinal Tract / Q000503:physiopathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010063:Ovum; D010919:Placebos; D012221:Rhinitis, Allergic, Perennial / Q000628:therapy*; D012307:Risk Factors; D013552:Swine / Q000469:parasitology*; D014258:Trichuris / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D010919:Placebos