title: Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study.
abstract: BACKGROUND
  Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.
  
  
  OBJECTIVE
  To determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms.
  
  
  METHODS
  Thirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks.
  
  
  RESULTS
  Mean maximum change in PD(10)AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval -1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups.
  
  
  CONCLUSIONS
  Hookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.
authors.affiliation: Division of Epidemiology and Public Health, University of Nottingham, UK. johanna.feary@nottingham.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Feary
authors.forename: A
authors.initials: A
authors.lastname: Venn
authors.forename: A
authors.initials: A
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Hooi
authors.forename: F H
authors.initials: FH
authors.lastname: Falcone
authors.forename: K
authors.initials: K
authors.lastname: Mortimer
authors.forename: D I
authors.initials: DI
authors.lastname: Pritchard
authors.forename: J
authors.initials: J
authors.lastname: Britton
mesh_terms: D000249:Adenosine Monophosphate / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000628:therapy; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D001985:Bronchial Provocation Tests; D003233:Conjunctivitis, Allergic / Q000628:therapy; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006725:Hookworm Infections / Q000150:complications* / Q000469:parasitology; D006801:Humans; D008297:Male; D010919:Placebos; D006255:Rhinitis, Allergic, Seasonal; D012449:Safety; D012882:Skin Tests; D006113:United Kingdom; D055815:Young Adult
chemical_list: D010919:Placebos; D000249:Adenosine Monophosphate