Hookworm-induced Hypersensitivity: A Response

Abstract

Since the recent discovery that the ubiquitous nematode parasite of dogs, Ancylostoma caninum, causes eosinophilic enteritis (EE) in people, research into zoonotic hookworm infections is enjoying a `rebirth'. The association between A. caninum (a parasite that is endemic in dogs throughout most of the tropic and sub-tropic regions of the world) and enteric disease in people, seemed to have escaped notice up until the late 1980s[1]. In this issue of Parasitology Today, John Croese has reviewed the subject in some detail, but appears to have omitted a key issue in our understanding (or lack thereof) of hookworm-mediated allergy. When considering the intense nature of the human allergic response to canine hookworms, Croese refers to A. caninum as a parasite that is poorly `adapted' to growth and survival in humans. His explanation centres on canine hookworms inducing allergy in people (characterized by IgE and eosinophilia) by inoculating into the mucosa, antigens that are either subtly different from, or not found at all, in anthropophilic hookworms leading to a lack of tolerance of this parasite. While at a glance this may appear to be a valid argument, Croese fails to mention crucial findings described in one of his references[2], where Maxwell and colleagues described the clinical and immunologic response of five volunteers to low dose infections with 50 infective larvae of the anthropophilic hookworm, Necator americanus. In this study, four of the patients complained of abdominal pain; the fifth, however, had such severe intestinal pain that the infection had to be treated and the experiment terminated. An interesting feature of this one patient's infection was an absence of eggs in the faeces, a notable feature of human enteric infection with A. caninum. Maxwell claimed that this finding was surprising based on the description by others of an association between gastrointestinal pain and heavy worm burdens[3, 4]. Another piece of evidence that does not support Croese's hypotheses actually comes from his own research; of nine patients where a solitary adult A. caninum was recovered, one had no gastrointestinal symptoms and underwent colonoscopy for anxiety about bowel cancer[5]; in addition, this patient mounted a strong IgG and IgE response to secretory antigens of the parasite. This finding suggests that a far greater proportion of the population may be asymptomatically infected with canine hookworms than first realized, lending support to the notion that A. caninum is no more likely to induce gut hypersensitivity in people than anthropophilic hookworms.