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DOSE-RANGING STUDY FOR TRIALS OF THERAPEUTIC INFECTION WITH NECATOR AMERICANUS IN HUMANS

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.

Received August 15, 2005. Accepted for publication June 23, 2006.

Acknowledgments: We thank the volunteers for participating in the study.

Disclosure: D. Pritchard wishes to disclose that he is an inventor on a patent supporting the use of molecules derived from nematodes as immune modulatory agents. The study could be viewed as supportive of such intellectual property if any ensuing trial is successful. This statement is made in the interest of full disclosure and not because the author considers this to be a conflict of interest.

^* Address correspondence to Johanna Feary, Division of Epidemiology and Public Health, University of Nottingham, Nottingham City Hospital, Nottingham NG5 1PB, United Kingdom. E-mail: johanna.feary{at}nottingham.ac.uk

Authors’ addresses: Kevin Mortimer and Sarah Lewis, Division of Respiratory Medicine, University of Nottingham Clinical Sciences Building, City Hospital Hucknall Road, Nottingham NG5 1PB, United Kingdom, Telephone: 441-115-823-1936, Fax: 441-115-823-1946. Alan Brown, Chris Jagger, and David Pritchard, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom Telephone: 441-115-951-6165. Fax: 441-115-951-5102. Johanna Feary, Marilyn Antoniak, and John Britton, Division of Epidemiology and Public Health, University of Nottingham Clinical Sciences Building, City Hospital Hucknall Road, Nottingham NG5 1PB, United Kingdom, Telephone: 441-115-823-1936, Fax: 441-115-823-1946.