Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial

Peter Bager; Christian Moliin Outzen Kapel; Allan Knud Roepstorff; Stig Milan Thamsborg; John Arnved; Steen Rønborg; Bjarne Kristensen; Lars K. Poulsen; Jan Wohlfahrt; Mads Melbye

doi:10.1371/journal.pone.0022346

Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial

Peter Bager, Christian Moliin Outzen Kapel, Allan Knud Roepstorff, Stig Milan Thamsborg, John Arnved, Steen Rønborg, Bjarne Kristensen, Lars K. Poulsen, Jan Wohlfahrt, Mads Melbye

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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. TRIAL REGISTRATION: University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

Original language	English
Journal	P L o S One
Volume	6
Issue number	8
Number of pages	11
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0022346
Publication status	Published - 2011

Keywords

Adult
Animals
Autoantibodies
Double-Blind Method
Female
Gastrointestinal Tract
Humans
Immunoenzyme Techniques
Immunoglobulin G
Immunotherapy
Male
Middle Aged
Ovum
Placebos
Rhinitis, Allergic, Perennial
Risk Factors
Swine
Trichuris

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trialFinal published version, 892 KB

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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. TRIAL REGISTRATION: University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.",

keywords = "Adult, Animals, Autoantibodies, Double-Blind Method, Female, Gastrointestinal Tract, Humans, Immunoenzyme Techniques, Immunoglobulin G, Immunotherapy, Male, Middle Aged, Ovum, Placebos, Rhinitis, Allergic, Perennial, Risk Factors, Swine, Trichuris",

author = "Peter Bager and Kapel, {Christian Moliin Outzen} and Roepstorff, {Allan Knud} and Thamsborg, {Stig Milan} and John Arnved and Steen R{\o}nborg and Bjarne Kristensen and Poulsen, {Lars K.} and Jan Wohlfahrt and Mads Melbye",

year = "2011",

doi = "10.1371/journal.pone.0022346",

language = "English",

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issn = "1932-6203",

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T1 - Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial

AU - Bager, Peter

AU - Kapel, Christian Moliin Outzen

AU - Roepstorff, Allan Knud

AU - Thamsborg, Stig Milan

AU - Arnved, John

AU - Rønborg, Steen

AU - Kristensen, Bjarne

AU - Poulsen, Lars K.

AU - Wohlfahrt, Jan

AU - Melbye, Mads

PY - 2011

Y1 - 2011

N2 - 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. TRIAL REGISTRATION: University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

AB - 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. TRIAL REGISTRATION: University hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

KW - Adult

KW - Animals

KW - Autoantibodies

KW - Double-Blind Method

KW - Female

KW - Gastrointestinal Tract

KW - Humans

KW - Immunoenzyme Techniques

KW - Immunoglobulin G

KW - Immunotherapy

KW - Male

KW - Middle Aged

KW - Ovum

KW - Placebos

KW - Rhinitis, Allergic, Perennial

KW - Risk Factors

KW - Swine

KW - Trichuris

U2 - 10.1371/journal.pone.0022346

DO - 10.1371/journal.pone.0022346

M3 - Journal article

C2 - 21829616

SN - 1932-6203

VL - 6

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

ER -

Symptoms after ingestion of pig whipworm Trichuris suis eggs in a randomized placebo-controlled double-blind clinical trial

Abstract

Keywords

UN SDGs

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