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Experimental human hookworm infection: a narrative historical review.

ABSTRACT: 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.

SUBMITTER: Chapman PR

PROVIDER: S-EPMC8659326 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Impact of experimental hookworm infection on the human gut microbiota.

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Controlled Human Hookworm Infection: Accelerating Human Hookworm Vaccine Development.

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| S-EPMC5952933 | biostudies-literature

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| S-EPMC3276555 | biostudies-literature

Experimental hookworm infection: a randomized placebo-controlled trial in asthma.

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From Codivilla to Ponseti: historical narrative review on clubfoot treatment in Italy.

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| S-EPMC8339829 | biostudies-literature

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Experimental infection with the hookworm, Necator americanus, is associated with stable gut microbial diversity in human volunteers with relapsing multiple sclerosis.

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| S-EPMC8048248 | biostudies-literature

Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

Project description:IntroductionCeliac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled.MethodsWe undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year).ResultsSuccessful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6]).DiscussionHookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

| S-EPMC7678792 | biostudies-literature

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