The effect of the humoral immune response on the weight and fecundity of the hookworm Necator americanus was examined in an endemically-infected human population. There was a highly significant negative correlation between total IgE levels and parasite weight and fecundity, after controlling for any effects of host age and hookworm burden. This correlation was present both at initial treatment and after 2 years' reinfection. There was a similar negative correlation between the number of eosinophils and hookworm weight and fecundity at initial treatment. Correlations with levels of specific antibodies to N. americanus excretory-secretory products were weaker and not significant, although there was a trend towards negative correlations with anti-ES IgE. This is the first field evidence for an effective human immune response to N. americanus. Although the mechanism of this effect is not clear, we suggest that total IgE levels reflected the level of Th2 cell activation.

SUMMARYReinfection with hookworm (Necator americanus ) following chemotherapy was studied over 2 years in a rural village in Madang Province, Papua New Guinea. The prevalence of hookworm infection had returned to pre-treatment levels after 2 years, and the geometric mean hookworm burden had returned to 58 % of the pre-treatment value. The rate of acquisition of adult worms was independent of host age, and was estimated as a geometric mean of 2-9-3-3 worms/host/year (arithmetic mean 79-8-9 worms/host/year). There was significant predisposition to hookworm infection; the strength of this predisposition did not vary significantly between age or sex classes.

The natural infection of a community with the hookworm Necator americanus induces a vigorous humoral response to both larval and adult parasite antigens. This response occurs in all five human antibody isotypes, and data are presented to show that, at the population level, isotypes respond differently, following chemotherapy and during reinfection, to changes in antigen stimulation. The differential response probably reflects the fact that the parasite, during the course of its life cycle, presents different amounts of antigens at different anatomical locations. It is suggested that IgG and IgM responses against adult excretory-secretory (ES) products most accurately reflect the efficacy of chemotherapy, and the load of resident adult infection, while IgG responses against larval somatic antigens reflect continuous exposure to infection. These hypotheses should now be tested, at the level of the individual, in a longitudinal manner using more closely spaced sampling intervals. This repetitive sampling, and the inclusion of a measure of the exposure of the population to infective stages, will allow more definitive conclusions to be made about the role of the immune response in controlling worm burdens.

In this paper we describe the relationship between antibodies to Necator americanus stage-specific antigens and parasite burden in an endemically-infected population in Papua New Guinea. Using an age-structured analysis, we show that the correlation coefficient between levels of IgG against adult worm excretory-secretory (ES) antigen and parasite burden declined significantly with host age from positive in younger hosts to significantly negative in older hosts. A trend towards similar patterns was present for anti-larval IgG both pretreatment and after reinfection, and for anti-ES IgM and anti-ES IgE pretreatment. These patterns are consistent with a role for these isotypes in a protective immune response, although parasite-induced immunosuppression may provide an alternate explanation. This is another demonstration of possibly protective responses to N. americanus infection.

Human IgE responses to helminth infections have been described as both problematic and beneficial, in that type 1 hypersensitivity to parasite infections can reputedly cause pathology and/or parasite expulsion, (Pritchard, Quinnell & Walsh 1995). In the present communication, we can report that the IgE response to helminth infections may be beneficial in a diagnostic sense, in that antibodies of this isotype showed minimal cross-reactivity against antigens from the parasites tested. This information may be of benefit to workers attempting to establish ELISA assays for the specific diagnosis of zoonotic hookworm infections, for example, Ancylostoma caninum (Croese 1988), particularly in regions where human hookworm infection is endemic.

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In this study we have demonstrated significantly elevated levels of circulating IgG autoanti-IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti-IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti-IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti-IgE (P = 0.0019) and IgG3 anti-IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory-secretory worm products; thus suggesting that anti-IgE synthesis is more related to polyclonal hyper IgE production than to antigen-specific IgE stimulation. No correlation was seen between IgG subclass anti-IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti-IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti-IgE is to provide the host with protection against immune complex- and IgE-mediated hypersensitivity reactions to parasitic antigens.

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