title: Dose-ranging study for trials of therapeutic infection with Necator americanus in humans.
abstract: Epidemiological studies suggest that a hookworm infection producing 50 eggs/gram of feces may protect against asthma. We conducted a dose-ranging study to identify the dose of hookworm larvae necessary to achieve 50 eggs/gram of feces for therapeutic trials of asthma. Ten healthy subjects without asthma or airway hyperresponsiveness to inhaled methacholine received 10, 25, 50, or 100 Necator americanus larvae administered double blind to an area of skin on the arm. Subjects were seen weekly for 12 weeks and were then treated with mebendazole. Skin itching at the entry site and gastrointestinal symptoms were common at higher doses. Lung function did not change. Levels of blood eosinophils and IgE increased transiently, and levels of IgG increased progressively. All doses resulted in at least 50 eggs/gram of feces in the eight subjects who completed the study. Infection with 10 N. americanus larvae is well tolerated, elicits a modest host eosinophil response, and is potentially suitable for use in preliminary clinical therapeutic trials.
authors.affiliation: Division of Respiratory Medicine, University of Nottingham, City Hospital, Nottingham, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Mortimer
authors.forename: Alan
authors.initials: A
authors.lastname: Brown
authors.forename: Johanna
authors.initials: J
authors.lastname: Feary
authors.forename: Chris
authors.initials: C
authors.lastname: Jagger
authors.forename: Sarah
authors.initials: S
authors.lastname: Lewis
authors.forename: Marilyn
authors.initials: M
authors.lastname: Antoniak
authors.forename: David
authors.initials: D
authors.lastname: Pritchard
authors.forename: John
authors.initials: J
authors.lastname: Britton
mesh_terms: D000328:Adult; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001249:Asthma / Q000469:parasitology / Q000517:prevention & control* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D006801:Humans; D007814:Larva / Q000378:metabolism; D007958:Leukocyte Count; D008875:Middle Aged; D009331:Necator / Q000276:immunology / Q000502:physiology*; D009332:Necatoriasis / Q000503:physiopathology; D010270:Parasite Egg Count; D016896:Treatment Outcome
chemical_list: D000947:Antigens, Helminth