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Intestinal helminths are among the most common infectious organisms of humans, particularly in tropical regions, and can induce the production of large quantities of IgE antibody. Part of this response is directed against the helminths own antigens, but a polyclonal stimulation also occurs that may increase the allergic reactivity toward environmental allergens. The importance of this in the symptomatology of asthma in these regions is, however, uncertain. In the present study we evaluated the effect of regular anthelminthic treatment with albendazol for 1 yr on a group of asthmatic patients in a zone in which these parasites are endemic. The number of asthmatic crises, need for maintenance therapy with inhaled steroids, and use of inhaled beta 2-agonists were compared both with those in the year prior to the study for the treated patients, and with those in a group of asthmatic subjects evaluated in parallel, but in whom the parasitic infections were not controlled. Significant improvement in all of these indicators of clinical status occurred in the treated group, not only for the period of anthelminth administration, but also for the year following. However, after 2 yr without treatment, the severity of asthma reverted to the initial state. No significant changes were observed in the control group over the entire period of evaluation. At the beginning of the study, the patients' pulmonary function was below the levels predicted for normal individuals, but this was not changed by the anthelminthic treatment. The patients' total serum IgE levels, which were elevated at the beginning of the study, were significantly diminished by the anthelminth administration, as were the specific IgE antibody levels and positivity in skin tests for immediate hypersensitivity to the common environmental allergen Dermatophagoides sp. However, the specific response to Ascaris lumbricoides, a common helminth in the area, was maintained despite treatment. These results indicate that intestinal helminthic infections can contribute to the clinical symptoms of asthma in an endemic situation. This may occur via a direct response to the parasite and/or a nonspecific potentiation of allergic reactivity to environmental allergens.

As some factors associated with the tropical environment can modify the expression of atopie disease, various indicators of allergic reactivity were compared between allergic and non-allergic subjects of different socio-economic level in Caracas, Venezuela (Lat. 10°N). The socio-economic levels considered were high (HSEL), medium-high (MSEL) or low (LSEL). As generally found in temperature climates, in the HSEL the total serum IgE levels of allergic patients were significantly greater than those of nonallergic individuals (geometric means of 274 vs 126 IU/ml, respectively), as were also the specific serum IgE antibody levels (55-6 vs 23-8% positive, respectively, for house dust). These results correlated closely with the skin-test reactivity of these subjects (60-3 vs 17-5% positive for house dust). In this group, the degree of intestinal helminthic infection was low (5-6% positive for Ascaris). In contrast, for the MSEL where the degree of parasitic infection was higher (13-0%), the total serum IgE levels were elevated in both allergic and non-allergic subjects (602 vs 363 IU/ml). Similarly, positivity for specific IgE antibody was high, and comparable between allergies and non-allergies of this group (61-5 vs 54-2%), as was also the case for skin-test reactivity (71-9 vs 60-4%). In the LSEL, parasitic infection was prevalent (47-6%), and the total serum IgE levels were markedly elevated, with little difference occurring between allergic and non-allergic individuals (2269 vs 1981 IU/ml). The positivity for specific IgE antibody was high, and effectively independent of the allergic state (75-6 vs 53-7%), but in contrast the skin test reactivity was relatively low (22-0 vs 9-8%). The lack of correlation between skin test and specific IgE results in this group appeared to have Correspondence: Dr Neil R. Lynch, Instituto de Biomedicina, Aptdo. 4043, Caracas lOlOA, Venezuela. N. R. Lynch et al. two causes. Firstly, although the frequency of positivity in specific IgE was high, only low grade antibody activity was detected. Secondly, studies ofskin reactivity indicated that some form of interference to target cell sensitization was occurring. The possible participation of helminth-induced polyclonally-increased IgE synthesis in the modification of allergic reactivity is discussed.

The diagnosis of human infection by Toxocara canis relies heavily upon serological tests, the specificity of which can be inadequate in regions of endemic helminthiasis. When different population groups of tropical Venezuela were evaluated using ELISA based upon Toxocara excretory-secretory antigen (TcESA), solid-phase adsorption of the sera with extracts of a wide variety of non-homologous parasites revealed the existence of significant cross-reactivity. This was effectively and conveniently overcome when the test sera were incubated in the presence of the soluble parasite extracts in a competitive inhibition ELISA. The mean reduction of ELISA values caused by pre-adsorption of the sera tested was 32.2%, and that caused by competitive inhibition was 42.3%, the effects of these two procedures being strongly correlated (r = 0.83). The magnitude of the reduction was inversely proportional to the actual ELISA value (r = -0.55), and ranged from a mean of 68.0% in sera from apparently healthy individuals of medium-high socio-economic level, down to 28.1% in heavily parasitized Amazon indians. Ascaris showed the greatest degree of cross-reactivity in these tests, although under conditions of competitive inhibition even sera with high levels of antibody against this parasite could be negative in Toxocara ELISA. Western blotting revealed a major 81,400 D component that was shared between Ascaris and TcESA. Our results indicate that the competitive inhibition of cross-reactivity by soluble non-homologous parasite extracts provides a convenient and economical means of increasing the specificity of ELISA for the determination of the seroprevalence of toxocariasis in tropical populations.

Infection by helminthic parasites can cause the polyclonal stimulation of IgE synthesis, possibly via an enhanced production of interleukin-4 (IL-4), and this has been suggested to influence the allergic reactivity of tropical populations where these parasites are endemic. We evaluated a group of urban slum children in Caracas, Venezuela, with a high prevalence of helminthic infection (70.8%), to establish the relationship between the elevated IgE levels (3696 IU/ml) induced by these parasites and various aspects of the allergic response. Although the absolute levels of IL-4 detected in the sera of these children were low (0.65 +/- 0.20 ng/ml), a strong positive correlation (r = 0.78) was found between these and serum IgE. The cutaneous immediate hypersensitivity reactivity to extracts of common environmental allergens was relatively low (17.5% to house dust), although that to Ascaris extract was moderately high (49.4%). Significant inverse correlations were found between total IgE levels and the different skin test reaction diameters, including Ascaris. The positivity of Prausnitz-Kustner passive transfer tests was low in this group (34%), with a strong inverse correlation (r = -0.75) being found between this and total IgE levels. Significant inverse correlations were also found between total IgE levels and specific IgE antibody to environmental allergens, and to Ascaris antigen. We suggest that the polyclonal production of IgE stimulated by helminthic infection can suppress the allergic response to environmental and parasite allergens via both mast cell saturation and inhibition of specific IgE production.

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