title: Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00671138.
authors.affiliation: Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: A James
authors.initials: AJ
authors.lastname: Daveson
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Jones
authors.forename: Soraya
authors.initials: S
authors.lastname: Gaze
authors.forename: Henry
authors.initials: H
authors.lastname: McSorley
authors.forename: Andrew
authors.initials: A
authors.lastname: Clouston
authors.forename: Andrew
authors.initials: A
authors.lastname: Pascoe
authors.forename: Sharon
authors.initials: S
authors.lastname: Cooke
authors.forename: Richard
authors.initials: R
authors.lastname: Speare
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Macdonald
authors.forename: Robert
authors.initials: R
authors.lastname: Anderson
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.forename: John
authors.initials: J
authors.lastname: Croese
mesh_terms: D000328:Adult; D000723:Ancylostomatoidea / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000378:metabolism; D002446:Celiac Disease / Q000150:complications* / Q000276:immunology / Q000469:parasitology*; D003710:Demography; D004311:Double-Blind Method; D004386:Duodenum / Q000473:pathology; D005260:Female; D006725:Hookworm Infections / Q000150:complications* / Q000276:immunology / Q000469:parasitology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D014908:Triticum / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010919:Placebos