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 beenattributed in part to enteric helminth infection. A pilot study ofexperimental infection with the hookworm Necator americanuswas undertaken among a group of otherwise healthy people with celiac diseaseto test the potential of the helminth to suppress the immunopathologyinduced by gluten.

Methods

In a 21-week, double-blinded, placebo-controlled study, we explored theeffects 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 stagehookworm larvae or placebo were performed at week-0 and -12 respectively. Atweek-20, a five day oral wheat challenge equivalent to 16 grams of glutenper day was undertaken. Primary outcomes included duodenal Marsh score andquantification of the immunodominant α-gliadin peptide (QE65)-specificsystemic interferon-γ-producing cells by ELISpot pre- and post-wheatchallenge.

Results

Enteric colonisation with hookworm established in all 10 cases, resulting intransiently painful enteritis in 5. Chronic infection was asymptomatic, withno effect on hemoglobin levels. Although some duodenal eosinophilia wasapparent, hookworm-infected mucosa retained a healthy appearance. In bothgroups, wheat challenge caused deterioration in both primary and severalsecondary outcomes.

Conclusions

Experimental N. americanus infection proved to be safe andenabled testing its effect on a range of measures of the human autoimmuneresponse. Infection imposed no obvious benefit on pathology.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00671138","term_id":"NCT00671138"}}NCT00671138