Experimental human hookworm infection: a narrative historical review.

In 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the first experimental human infection, reported in 1901. Experimental human infections undertaken in the 20th century enabled understan...

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Main Authors: Paul R Chapman, Paul Giacomin, Alex Loukas, James S McCarthy
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-12-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009908&type=printable
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author Paul R Chapman
Paul Giacomin
Alex Loukas
James S McCarthy
author_facet Paul R Chapman
Paul Giacomin
Alex Loukas
James S McCarthy
author_sort Paul R Chapman
collection DOAJ
description In 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the first experimental human infection, reported in 1901. Experimental human infections undertaken in the 20th century enabled understanding of the natural history of infection and the immune response. More recently, experimental hookworm infection has been performed to investigate the immunomodulatory potential of hookworm infection and for the evaluation of hookworm vaccines and chemotherapeutic interventions. Experimental human hookworm infection has been proven to be safe, with no deaths observed in over 500 participants (although early reports predate systematic adverse event reporting) and no serious adverse events described in over 200 participants enrolled in contemporary clinical trials. While experimental human hookworm infection holds significant promise, as both a challenge model for testing anti-hookworm therapies and for treating various diseases of modernity, there are many challenges that present. These challenges include preparation and storage of larvae, which has not significantly changed since Harada and Mori first described their coproculture method in 1955. In vitro methods of hookworm larval culture, storage, and the development of meaningful potency or release assays are required. Surrogate markers of intestinal infection intensity are required because faecal egg counts or hookworm faecal DNA intensity lack the fidelity required for exploration of hookworm infection as a vaccine/drug testing platform or as a regulated therapy.
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spelling doaj-art-5359928cefc7400693d648e5c32053dc2025-08-20T02:46:28ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352021-12-011512e000990810.1371/journal.pntd.0009908Experimental human hookworm infection: a narrative historical review.Paul R ChapmanPaul GiacominAlex LoukasJames S McCarthyIn 1896, a serendipitous laboratory accident led to the understanding that hookworms propagate infection by penetrating skin, a theory that was then confirmed with the first experimental human infection, reported in 1901. Experimental human infections undertaken in the 20th century enabled understanding of the natural history of infection and the immune response. More recently, experimental hookworm infection has been performed to investigate the immunomodulatory potential of hookworm infection and for the evaluation of hookworm vaccines and chemotherapeutic interventions. Experimental human hookworm infection has been proven to be safe, with no deaths observed in over 500 participants (although early reports predate systematic adverse event reporting) and no serious adverse events described in over 200 participants enrolled in contemporary clinical trials. While experimental human hookworm infection holds significant promise, as both a challenge model for testing anti-hookworm therapies and for treating various diseases of modernity, there are many challenges that present. These challenges include preparation and storage of larvae, which has not significantly changed since Harada and Mori first described their coproculture method in 1955. In vitro methods of hookworm larval culture, storage, and the development of meaningful potency or release assays are required. Surrogate markers of intestinal infection intensity are required because faecal egg counts or hookworm faecal DNA intensity lack the fidelity required for exploration of hookworm infection as a vaccine/drug testing platform or as a regulated therapy.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009908&type=printable
spellingShingle Paul R Chapman
Paul Giacomin
Alex Loukas
James S McCarthy
Experimental human hookworm infection: a narrative historical review.
PLoS Neglected Tropical Diseases
title Experimental human hookworm infection: a narrative historical review.
title_full Experimental human hookworm infection: a narrative historical review.
title_fullStr Experimental human hookworm infection: a narrative historical review.
title_full_unstemmed Experimental human hookworm infection: a narrative historical review.
title_short Experimental human hookworm infection: a narrative historical review.
title_sort experimental human hookworm infection a narrative historical review
url https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0009908&type=printable
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