Infection by Ascaris lumbricoides and bronchial hyper reactivity: an outstanding association in Venezuelan school children from endemic areas.

Asthma and other respiratory diseases have increased in the last years among Venezuelan children from helminthic endemic areas where the infection by Ascaris lumbricoides has been associated to bronchial airway inflammation in parasitized individuals. The aim of this work was to investigate the possible associations between the development of bronchial hyper reactivity and the immune response against A. lumbricoides in urban and rural children. We evaluated 470 school children from rural and urban communities. Pulmonary function tests were performed and >or=20% PC(20) changes were considered as a positive diagnostic of bronchial hyper reactivity. The prevalence and intensity of A. lumbricoides infection was determined by faecal examination. Specific serum IgE levels using a modified ELISA and skin prick tests against A. lumbricoides and the common allergen Dermatophagoides pteronyssinus were done. The number of circulating lymphocyte sub populations was determined by flow cytometry analysis. In rural children, bronchial hyper reactivity was associated with increased specific levels of anti-A. lumbricoides IgE (p<0.0001) and skin test positivity for A. lumbricoides (p<0.0001). The percentage of FEV1 predictive values correlated inversely (p<0.0001) with anti-A. lumbricoides IgE levels. Elevated numbers of circulating CD3+CD4+ and CD20+CD23+ cells were found in rural children with bronchial hyper reactivity compared to their asymptomatic counterparts. They correlated positively with anti-A. lumbricoides IgE levels (p<0.005 and <0.0001, respectively). In contrast, in urban children, bronchial hyper reactivity was associated with elevated anti-D. pteronyssinus IgE levels (p=0. 0089), skin hyper reactivity towards this aero allergen (p=0.003) and to an increase in the number of CD3+CD8+ (p<0.0001). Our results suggest that the IgE response against A. lumbricoides infection may be involved in the development of bronchial hyper reactivity among rural children from endemic areas and also that improved hygienic conditions in the urban environment is associated with increased responses to airborne allergens.

[Influence of helminthic infections and nutritional status on immune response in Venezuelan children]. / Influencia de las infecciones helmínticas y el estado nutricional en la respuesta inmunitaria de niños venezolanos.

We investigated the influence of nutritional status, as determined from anthropometric measurement, and of helminthic infections on the immune response of children of low socioeconomic status in two rural communities in Venezuela: El Cardón in the state of Nueva Esparta and San Daniel in the state of Miranda. A total of 125 boys and girls between 2 and 15 years old participated in the study. Their socioeconomic stratum was determined by a modified Graffar method. A physical examination was performed, as was also an anthropometric evaluation that took into account three indicators--weight-for-height, weight-for-age, and height-for-age--according to parameters established by the World Health Organization. Other examinations included feces, secretory IgA in saliva, total serum IgE, and anti-Ascaris-specific immunoglobulins. The children in both of the communities were in strata IV and V of the of Graffar scale, with a significantly greater number of stratum V inhabitants in San Daniel (P < 0.001). The results suggest that exposure level and individual susceptibility to the parasites are determining factors in parasitic infection and immune system behavior. The intensity of the parasitic burden plays an important role in stimulating polyclonal IgE, which diminishes the effectiveness of the specific response to those infections. On the other hand, nutritional deficiencies could change the immune mechanisms of the mucous membranes, negatively influence the synthesis of secretory IgA, and stimulate the production of polyclonal IgE. Poor sanitary and socioeconomic conditions promote more exposure to gastrointestinal parasites and a deficient nutritional status, which modulates the immune response and affects serum IgE and secretory IgA production mechanisms.

Immunological changes associated with clinical improvement of asthmatic children subjected to psychosocial intervention.

In the present study we evaluated the impact of a program of psychosocial intervention (PSI) on the immunological status and the clinical management of a group of asthmatic children of an island population in Venezuela. We studied a total of 35 asthmatic children who belonged to either a PSI group (19 patients) or a control group (16 patients), both of which received conventional antiasthmatic treatment. The PSI group received, in addition, a 6-month psychosocial intervention program which included relaxation, guided imagery, and self-esteem workshops. During the PSI period, the number of asthmatic episodes and the use of bronchodilator medication were significantly reduced, and pulmonary function was significantly improved, compared to the 6 months before intervention. There was also a significant reduction in the specific IgE responses against the most important allergen in these children, the intestinal parasite Ascaris lumbricoides. PSI resulted in a significant increase of NK cells, an augmented expression of the T-cell receptor for IL-2, and a significant decrease of leukocytes with low affinity receptors for IgE. In fact, these surface markers became similar to those of nonasthmatic children from both Coche Island and the mainland. None of these clinical or immunological changes were seen in the control group of asthmatics who did not undergo PSI. These results are consistent with the possibility that PSI induces immunological alterations that are responsible for the clinical and physiological improvements observed in the study group.

Association of polymorphisms in the beta2-adrenoreceptor gene with higher levels of parasitic infection.

The diminishing incidence of parasitic infection in westernised societies has been suggested to result in an increased prevalance of asthma. Asthma is a polygenic disease and genome screens have shown that genes on chromosome 5q31-33 are strongly linked to the disease. The gene for the beta2-adrenoreceptor is located in this region and two polymorphisms have been identified that result in amino acid changes at positions 16 (ArgGly) and 27 (GlnGlu). To determine whether these polymorphisms influence asthma and parasitic infection, a genotype/phenotype study has been performed on a cohort of 126 children from Coche Island in Venezuela. There is a high incidence of asthma on the island and intestinal helminthiasis is endemic. Genotyping for both polymorphisms was carried out by using the polymerase chain reaction and allele-specific oligonucleotide hybridisation. Genotype frequencies in this cohort were consistent with other studies and both polymorphisms were in significant linkage disequilibrium. Individuals who were homozygous for Arg16 had significantly higher levels of specific IgE to Ascaris lumbricoides (P=0.002), significantly higher A. lumbricoides egg counts (P<0.001) and significantly larger wheal sizes following skin-prick testing with A. lumbricoides allergen (P=0.008). There was no association between either polymorphism and total serum IgE or asthma in this population. A combination of mast cell degranulation and the lung migratory phase of A. lumbricoides larvae may result in bronchoconstriction in infected individuals. These results suggest that the Gly 16 allele confers resistance to high levels of parasitic infection in this population. An alternative explanation for the association is that it may be the result of linkage disequilibrium with other genes in the chromosome 5q31-33 region.

Relationship between helminthic infection and IgE response in atopic and nonatopic children in a tropical environment.

BACKGROUND: Although IgE antibody is clearly involved in allergic reactions to environmental allergens, this immunoglobulin is an important component of host-protective immune responses against the helminthic parasites that are endemic in the majority of the world population. However, these infections not only stimulate the production of antiparasite IgE antibody but can nonspecifically induce polyclonal IgE synthesis that results in highly elevated total serum IgE levels. Such polyclonal stimulation can diminish specific IgE antibody responses and cause saturation of mast cell Fc epsilon receptors, thus inhibiting allergic reactivity. This may represent a mechanism of immune evasion by the parasite. OBJECTIVE: Because an atopic disposition is generally recognized to be associated with elevated IgE synthesis against environmental allergens, the aim of this study was to evaluate the influence of atopy on the antiparasite response. To this end, we examined two groups of Venezuelan children in whom the intestinal helminth Ascaris lumbricoides is endemic but that differ greatly in their level of atopy. One group was from an island population (Coche Island) that has a very strong atopic background and in which the prevalence of allergic disease is extremely high. The other was a group of nonatopic children belonging to a mainland population (Barrio Los Erasos) that is of comparable socioeconomic level and has an exposure to helminthic infection similar to that of the island group but a relatively low expression of allergic diseases. RESULTS: Although the living conditions and the prevalence of Ascaris infection of the two groups were comparable, the intensity of the parasitic infection was considerably higher in the nonatopic mainland children (geometric mean values of eggs per gram of feces: Barrio Los Erasos, 7621; Coche Island, 1435; p < 0.001). In addition, their total serum IgE levels were significantly more elevated than in the atopic island group (geometric mean: Barrio Los Erasos, 2172; Coche Island, 941 IU/ml; p < 0.001). In contrast, the specific anti-Ascaris response was much stronger in the atopic children (geometric mean: Barrio Los Erasos, 0.30; Coche Island, 0.91 PRU/ml; p < 0.001), which resulted in the ratio of specific to total IgE being nine times higher than in the nonatopic mainland subjects. These differences were maintained even when the children were matched on the basis of infection intensity, thus indicating that the atopic children have an intrinsic propensity to favor specific over polyclonal IgE responses to the parasite. CONCLUSIONS: The children with a strong atopic background demonstrated IgE responses concordant with an enhanced protective response against helminthic parasites and had significantly lower intensities of infection than their nonatopic counterparts. These observations support the concept that the atopic state has conferred a selective evolutionary advantage that could compensate for its involvement in allergic disease.

Clinical improvement of asthma after anthelminthic treatment in a tropical situation.

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.

Mutation screening of interferon-gamma (IFNgamma) as a candidate gene for asthma.

BACKGROUND: Reduced levels of interferon gamma (IFNgamma) mRNA and protein have been detected in the bronchoalveolar lavage fluid of atopic asthmatics. IFNgamma is secreted by TH1 cells while IL-4 and IL-5 are secreted by TH2 cells and an imbalance in the TH1/TH2 response may be responsible for atopic asthma. The gene for IFNgamma is located on chromosome 12; a region of the genome which has been shown in linkage studies to be associated with asthma. OBJECTIVE: To determine if there are any mutations present in the coding exons and 5' flanking region of the IFNgamma gene in atopic asthmatic subjects compared with controls to explain the lower levels of this cytokine as an inherited, rather than acquired, factor in the asthmatic subjects. METHODS: The four exons and 5' flanking region of the IFNgamma gene were amplified by polymerase chain reaction (PCR) from genomic DNA of 265 individuals from a Western Australian and a Venezuelan population. The PCR products were examined by single strand conformational polymorphism and heteroduplex analyses to see if there were any changes in the DNA migration patterns which would suggest the presence of a sequence variation. RESULTS: The four exons and the 5' flanking region of the IFNgamma gene were amplified from 265 individuals from two populations. Single strand conformational polymorphism and heteroduplex analyses did not reveal any mutations in the regions examined. CONCLUSION: The gene for IFNgamma appears to be highly conserved as no sequence variations were detected in 265 individuals. These results suggest that mutations of the IFNgamma gene are unlikely to be a significant cause of an inherited asthma diathesis.