Background and Aims: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten

A. James Daveson

Alex Loukas

Andrew Clouston

Andrew Pascoe

C Catassi

C Maxwell

D Blount

DA Leffler

DE Elliott

Dianne M. Jones

DM Altmann

ED Palmer

Graeme A. Macdonald

H Aoyama

Henry McSorley

J Correale

J Croese

J Feary

J Glas

J Tye-Din

JA Jackson

James S. McCarthy

JF Bach

John Croese

JR Feary

JV Weinstock

K Mortimer

Lise Lotte Gluud

M Fumagalli

MF Kagnoff

MN Marsh

NE Ruyssers

P Bager

P Musgrove

PC Beaver

PH Green

PJ Hotez

Richard Speare

RJ Quinnell

Robert Anderson

RP Anderson

RW Summers

Sharon Cooke

Soraya Gaze

V Wright

English

PubMed

BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten.



METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd) stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge.



RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes.



CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology

Daveson, A. James

Jones, Dianne M.

Gaze Jangola, Soraya

McSorley, Henry

Clouston, Andrew

Pascoe, Andrew

Cooke, Sharon

Speare, Richard

Mcdonald, Graeme A.

Anderson, Robert

McCarthy, James S.

Loukas, Alex

Croese, John

ResearchOnline at James Cook University

Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial


                        was undertaken among a group of otherwise healthy people with celiac disease
                        to test the potential of the helminth to suppress the immunopathology
                        induced by gluten. stage
                        hookworm larvae or placebo were performed at week-0 and -12 respectively. At
                        week-20, a five day oral wheat challenge equivalent to 16 grams of gluten
                        per day was undertaken. Primary outcomes included duodenal Marsh score and
                        quantification of the immunodominant α-gliadin peptide (QE65)-specific
                        systemic interferon-γ-producing cells by ELISpot pre- and post-wheat
                        challenge.Enteric colonisation with hookworm established in all 10 cases, resulting in
                        transiently painful enteritis in 5. Chronic infection was asymptomatic, with
                        no effect on hemoglobin levels. Although some duodenal eosinophilia was
                        apparent, hookworm-infected mucosa retained a healthy appearance. In both
                        groups, wheat challenge caused deterioration in both primary and several
                        secondary outcomes. infection proved to be safe and
                        enabled testing its effect on a range of measures of the human autoimmune
                        response. Infection imposed no obvious benefit on pathology

Daveson A. James

Jones Dianne M.

Gaze Soraya

McSorley Henry

Clouston Andrew

Pascoe Andrew

Cooke Sharon

Speare Richard

Macdonald Graeme A.

Anderson Robert

McCarthy James S.

Loukas Alex

Croese John

Public Library of Science (PLOS)

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease
                    – A Randomised Double-Blinded Placebo Controlled Trial

Crossref

PLoS ONE

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial

The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten.In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd) stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge.Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes.Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology.ClinicalTrials.gov NCT00671138

A James Daveson

Dianne M Jones

Graeme A Macdonald

James S McCarthy

Directory of Open Access Journals

Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial.

ResearchOnline@JCU

Gaze, Soraya

Macdonald, Graeme A.

University of Queensland eSpace

Effect of hookworm infection on wheat challenge in celiac disease - A randomised double-blinded placebo controlled trial

BACKGROUND AND AIMS: The association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten. METHODS: In a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-naïve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd) stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant α-gliadin peptide (QE65)-specific systemic interferon-γ-producing cells by ELISpot pre- and post-wheat challenge. RESULTS: Enteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes. CONCLUSIONS: Experimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology. TRIAL REGISTRATION: ClinicalTrials.gov NCT00671138

Daveson, AJ

Jones, DM

Gaze, S

McSorley, H

Clouston, A

Pascoe, A

Cooke, S

Speare, R

Macdonald, GA

Anderson, R

McCarthy, JS

Loukas, A

Croese, J

University of Melbourne Institutional Repository

Effect of hookworm infection on wheat challenge in celiac disease - a randomised double-blinded placebo controlled trial

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https://figshare.com/articles/Effect_of_Hookworm_Infection_on_Wheat_Challenge_in_Celiac_Disease____A_Randomised_Double_Blinded_Placebo_Controlled_Trial/138432

Effect of Hookworm Infection on Wheat Challenge in Celiac Disease – A Randomised Double-Blinded Placebo Controlled Trial

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