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 (3rd 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.Trial registrationUniversity hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

Helminth Infections and Host Immune Regulation

“…Finally, good quality controls are often unavailable, if they are used at all. Where blinded matched controls are used, participants may realize that they are infected due to mild symptoms associated with infection, such as skin rash, cough, and gastrointestinal symptoms (20,205). A placebo effect is therefore difficult to discount in many trials.…”

“…suis is a swine parasite that is not adapted to humans and causes significant side effects, including gastrointestinal upset and diarrhea (20). These symptoms appear to abate after several weeks of treatment, implying a suppression of the inflammatory response in the gut during chronic stimulation.…”

From the worm to the pill, the parasitic worm product ES-62 raises new horizons in the treatment of rheumatoid arthritis

“…[78][79][80] Treatment with T. suis eggs skews the immune response towards the modified Th2 phenotype with increased IL-10 production, and it has proven to be relatively safe, with only some minor adverse effects reported, such as gastrointestinal reactions. 81 However, rather than exploiting live worms that are pathogens, a defined immunomodulatory product like ES-62 might be more suitable for drug development than whole worms or their eggs. Nevertheless, ES-62 still presents important limitations that prevent its translation to the clinic.…”

Trichuris suis ova: Testing a helminth-based therapy as an extension of the hygiene hypothesis

“…[26][27][28][29] The subjects received placebo or TSO, 8 doses of 2500 eggs, at 3-week intervals. Mild gastrointestinal side effects were reported in 47% of TSO-treated subjects but also in 32% of placebo-treated subjects.…”

“…A phase 2b double-blind, randomized, placebo-controlled trial in 100 adults with seasonal allergic rhinitis was performed in Denmark. [26][27][28][29] The subjects received placebo or TSO, 8 doses of 2500 eggs each, at 3-week intervals. There was no difference in daily symptom scores (runny, itchy, and sneezing nose) or in the percentage of well days during the grass pollen season between the TSO and control groups.…”