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Am. J. Trop. Med. Hyg., 78(6), 2008, pp. 936-945
Copyright © 2008 by The American Society of Tropical Medicine and Hygiene

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Development of a Model of Hookworm Infection Exhibiting Salient Characteristics of Human Infection

Gareth D. Griffiths, Alan P. Brown*, Doreen S. W. Hooi, Peter C. Pearce, Rebecca J. Hornby, Leah Scott, AND David I. Pritchard
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire, United Kingdom; The Boots Science Building, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom

Patent and pathologic infections of the human hookworm Necator americanus were established in the common marmoset (Callithrix jacchus). In a pilot study, a laboratory strain of N. americanus was compared with a fresh field isolate. Pathology was more severe in animals infected with a fresh isolate. In all animals, infection was associated with increased total plasma IgE and production of IgG specific to adult worm excretory/secretory (ES) products. Histamine was released by basophils in response to IgE, ES products, and a recombinant hookworm allergen, calreticulin. The pilot study indicated the potential of this animal model of hookworm infection and led us to investigate the consequences of infecting a further cohort with the fresh field isolate. This second study confirmed our initial findings, that it is possible to investigate the human hookworm N. americanus in a model exhibiting many of the characteristics of the immunology of hookworm infection in its definitive host.

Received December 1, 2005. Accepted for publication January 31, 2008.

Acknowledgments: We thank Neil Hughes, Bob Knight, and Jan Platt for support and advice in preparation and processing of tissue samples for pathologic analysis and photomicrographs; Arthur Baskerville for advice on interpretation of pulmonary pathologic changes; and Ed Gosden and Keith Male for hematologic analysis. Financial support: This work was supported by the Wellcome Trust and the Defence Science and Technology Laboratory.

* Address correspondence to Alan P. Brown, The Boots Science Building, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, United Kingdom. E-mail: alan.brown{at}nottingham.ac.uk

Authors’ addresses: Gareth D. Griffiths, Peter C. Pearce, Rebecca J. Hornby, and Leah Scott, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom, Tel: 44-1980-613-367, Fax: 44-1980-613-741. Alan P. Brown, Doreen S. W. Hooi, and David I. Pritchard, The Boots Science Building, School of Pharmacy, University of Nottingham, NG7 2RD, Nottingham, United Kingdom, Tel: 44-115-951-6165/846-6292, Fax: 44-115-951-5122.






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