Allergy controls the population density of necator americanus in the small intestine

Background&Aims: Nearly 700 million people remain infected with hookworms. Although allergy is intuitively linked to immunity against helminths, few positive examples have been characterized. Larval migration through the lungs has been considered the likely interface at which hookworm attrition occurs. As part of a study evaluating a potential role for hookworms in the modulation of human autoimmunity, we examined parasite migration and intestinal colonization. Methods. Capsule and conventional endoscopies supplemented the evaluation of healthy volunteers and Crohn's disease patients recently inoculated with larvae of the human hookworm Necator americanus. Two healthy volunteers with a previously established and stable hookworm infection were inoculated with 50 larvae and had serial capsule endoscopies performed. Results: Eosinophilic enteritis developed in all subjects after the initial inoculation. Newly inoculated larvae in the 2 subjects with an established infection reliably reached the intestine within 4 weeks. Thereafter, the colony diminished to the host's constitutive status quo because mostly immature worms failed to attach. The intensity of the eosinophilic response correlated negatively with the time available for hookworms to feed and positively with hookworm attrition. Conclusions: Necator larval migration to the intestine is uncontested. We propose that allergic inflammation purposefully degrades the hookworm's bite, causing premature detachment, restricted feeding, and expulsion. This novel biological dynamic suggests a new paradigm of hookworm resistance.