Co-infection with Ascaris lumbricoides modulates protective immune responses against Giardia duodenalis in school Venezuelan rural children.

We evaluated the effect of Ascaris lumbricoides on Giardia duodenalis infection and TH1/TH2 type immune mechanisms toward this parasite in 251 rural parasitized and 70 urban non-parasitized school children. The children were classified according to light (0-5000 eggs/g faeces) or moderate (>5001-50,000 eggs/g faeces) A. lumbricoides infection. Anti G. duodenalis skin hyper-reactivity, IgE, IgG, IL-13, IFN γ, IL6 and IL-10 levels were compared among G. duodenalis infected and non-infected children according to light or moderate A. lumbricoides infection. It was found that 62% of the A. lumbricoides moderately infected children were co-infected by G. duodenalis compared to 45% of the lightly infected group. After treatment, 42% of the A. lumbricoides moderately group were infected with G. duodenalis compared to 11% of their lightly counterparts, being A. lumbricoides IL-10 levels higher (p<0.0001) in the moderately infected group. In the A. lumbricoides lightly parasitized children, G. duodenalis infection was associated to a significant increase (p<0.005) of the levels of G. duodenalis IL-13, IFN-γ, IL-6, IgE, IgG and skin test hyper reactivity. In contrast, there was no effect of G. duodenalis infection in the elevation of these parameters among the A. lumbricoides moderately parasitized group, being those levels similarly lower as those observed in the control group. Inverse correlations were found between the levels of anti G duodenalis antibodies, skin test hyper-reactivity and cytokines with the intensity of A. lumbricoides infection (p>0.0001) and A. lumbricoides IL-10 levels (p>0.0001), suggesting that co-infection with A. lumbricoides may affect both TH1 and TH2 type immunity against G. duodenalis that may play an important role in the susceptibility to the infection after chemotherapy in children from endemic areas.

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.

Importance of including Blomia tropicalis in the routine diagnosis of Venezuelan patients with persistent allergic symptoms.

BACKGROUND: Blomia tropicalis is a common mite found in the house dust of many tropical countries including Venezuela. The prevalence of skin test and specific serum immunoglobulin (Ig)E reactivity to B. tropicalis in Venezuela has not been previously evaluated. METHODS: In the present study we evaluated the skin reactivity by skin prick test and specific IgE by a multiple antigen blot assay, against B. tropicalis and Dermatophagoides pteronyssinus, in a group of 115 subjects who attended the Allergy Clinic of the Institute of Biomedicine, Caracas, Venezuela, and we studied possible cross reactions between similar proteins of these two mites. RESULTS: One hundred and six patients with persistent allergic respiratory symptoms showed a positive skin prick test to at least one of the mite extracts, with the frequency of positive reactions to B. tropicalis being as high as to D. pteronyssinus. Twelve patients reacted only to D. pteronyssinus and 13 different patients only to B. tropicalis. Specific IgE to each of the mite extracts was found with similar frequency, and the results coincided with the skin test reactivity. CONCLUSIONS: The study indicated the importance of including B. tropicalis in routine diagnostic testing in tropical and sub-tropical situations.

Defective regulation of the protective IgE response against intestinal helminth Ascaris lumbricoides in malnourished children.

It is well established that malnutrition affects the immune response and increases the susceptibility to parasitic infection. In the present study we evaluated some aspects of the cellular and cytokine network that regulate the IgE responses, which are important components of host defence mechanisms against helminthic parasites in children infected with the intestinal helminth Ascaris lumbricoides, and with differing degrees of malnutrition. We found a defective T cell response in malnourished children, as indicated by diminished levels of circulating total (CD3+), helper (CD4+), IL-2-receptor-bearing (CD4+CD25+) and memory helper T cell responses (CD4+CD45RO+) in keeping with the decreased specific IgE levels against Ascaris lumbricoides. In contrast, the proportions of total B cells (CD20+), and those bearing the low-affinity IgE receptor (CD23+) were increased in the moderated malnourished children. Moreover, serum IL-4 levels and total IgE were also increased in these children. We suggest that malnutrition can cause an imbalance in T cell subpopulations that may lead to a defective T cell maturation and a decreased specific anti-Ascaris IgE response thus increasing the susceptibility to such infections. The high levels of total IgE observed may be related to a non-specific stimulation of the proliferation of activated B cells, probably caused by helminthic parasites and other infectious agents that are frequent in malnourished children.

[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.

Helminthic infection and anthropometric indicators in children from a tropical slum: Ascaris reinfection after anthelmintic treatment.

We evaluated helminthic infection and anthropometric indicators of nutritional status in a group of school-age children from a slum area of Caracas, Venezuela. The proportions of children at or below the 10th percentiles for height/age and weight/age were significantly higher in those presenting helminthiasis than in those uninfected. Although this could partially reflect a codependence of both helminthic infection and undernutrition or poverty, when the children were administered regular anthelmintic treatment for a year their anthropometric values improved significantly. When they were re-evaluated 8 months after the end of anthelmintic administration, the degree of reinfection by the most common helminth, Ascaris lumbricoides, was significantly higher in the growth-retarded children. These results confirm the relationship between helminthic infection and decreased growth rates in underprivileged populations, and indicate that children at nutritional risk are more susceptible to such infections, even after a prolonged parasite-free period.

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.

Association between giardiasis and allergy.

BACKGROUND: Previous studies have indicated that there may be an association between infection by the intestinal protozoan Giardia lamblia and the expression of allergic disease. OBJECT: We evaluated a group of children who attended the Outpatient Clinic of the Children's Hospital in Caracas, Venezuela, a group in which both allergic disease and giardiasis were common. METHODS: We performed feces examination and measured total and specific serum IgE (immunoglobulin E) in these children. RESULTS: We found that 70% of the children infected with G. lamblia presented symptoms of allergy, in contrast to 43% of the non-Giardia parasitized group (P <.05). In addition, the G. lamblia parasitized children showed significantly higher levels of total serum IgE (1194 IU/mL) than the non-Giardia group (822 IU/mL) (P <.005). Children infected with G. lamblia showed higher levels of specific serum IgE antibody against food allergens compared both with the non-parasitized group (P <.0001) and children infected with parasites other than Giardia (P <.05). In contrast, IgE responses against the house dust mite Dermatophagoides pteronyssinus were similar in all the groups studied. CONCLUSIONS: These results reveal a clear relationship between giardiasis and allergy, possibly because infection by this protozoon enhances sensitization towards food antigens, due to increased antigen penetration through damaged intestinal mucosa.

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.

Nutritional status and the IgE response against Ascaris lumbricoides in children from a tropical slum.

Helminthic infection can stimulate the interleukin-4 (IL-4)-dependent polyclonal synthesis of immunoglobulin E (IgE) in children endemically exposed to these parasites. As such children are also frequently at nutritional risk, in this study we considered the possible influence of malnutrition on serum IL-4 levels and the IgE response in helminthic infection. We evaluated 85 Ascaris-infected children living in an urban slum area of Caracas, Venezuela, and found that the serum levels of IL-4 and total IgE were significantly higher in malnourished children than in their well nourished counterparts. In contrast, the specific anti-Ascaris IgE antibody response was significantly lower in the malnourished group. After anthelmintic treatment of the children, the total serum IgE and IL-4 levels decreased significantly in the well nourished group, while the specific anti-Ascaris IgE antibody response increased. No significant change was detected, however, in the malnourished group. Our results suggested that malnutrition potentiates the polyclonal stimulation of IgE synthesis induced by helminths. As specific IgE antibody has been implicated in the resistance to helminthic infection, and the polyclonal stimulus diminishes this response, these factors may increase the susceptibility of malnourished children to such parasites.

Ascaris reinfection of slum children: relation with the IgE response.

Total and Ascaris-specific serum IgE levels were measured in a group of 98 Ascaris-infected children from a slum area of Caracas, Venezuela, in whom the infections were eliminated by regular treatment for 22 months with the anthelmint Oxantel/Pyrantel ('Quantrel'). The children were re-evaluated at the end of the treatment programme, and then 8 months later, at which time reinfection was assessed. Total IgE levels at the beginning of the study were significantly higher in the children who became reinfected after treatment, compared with those who did not. The anthelmint treatment caused a significant decrease in the total IgE levels in most of the children, and after a period of 8 months without treatment these continued to decrease in the non-reinfected group, but increased again in the reinfected children. The reverse pattern was found for Ascaris-specific IgE antibody levels, and in fact an inverse correlation was found between total and anti-Ascaris IgE levels. Striking associations were found between reinfection and high pretreatment values of total IgE, but low levels of specific IgE antibody. These data support the concept that specific IgE antibody may participate in the protection against helminthic infection, and suggest that the polyclonal stimulation of IgE synthesis caused by these parasites may reduce the effectiveness of such responses. The results also indicate that different individuals have varying propensities to respond polyclonally to the helminths, and this influences their resistance to infection.

Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum.

It is well known that helminthic infection can cause a polyclonal stimulation of the synthesis of IgE, which is dependent on interleukin-4 (IL-4) production, and it has been suggested that this can modulate the expression of allergic reactivity in tropical populations. We evaluated the effect of regular anthelmintic treatment, for a period of 22 months, on certain aspects of the allergic reactivity of children in a slum area of Caracas, Venezuela, where helminths are endemic. The treatment (Oxantel-Pyrantel; Quantrel) effectively eliminated intestinal helminthic infection and resulted in a significant decrease in the initially elevated total serum IgE levels. IL-4 was detectable in the serum, and a significant reduction in IL-4 was also observed after treatment. In contrast, both the immediate-hypersensitivity skin-test reactivity and serum levels of specific IgE antibody against environmental allergens were markedly increased in the treated children. In a group of children who were also evaluated in the same slum, but who declined treatment, a substantial increase in helminthic infection occurred, which was related to an acute deterioration of the socioeconomic conditions of Venezuela over the course of our study period. This was paralleled by a considerable increase in total IgE levels in these children and a decrease in the skin-test reactivities and specific IgE levels. The application of Prausnitz-Küstner passive transfer tests and analysis of specific IgE antibody levels indicated that the polyclonal stimulation of IgE synthesis by helminthic parasites results in mast cell Fc epsilon receptor saturation and suppression of specific IgE antibody synthesis. This inhibition of allergic reactivity is reversible by anthelmintic treatment.

Modulation of the allergic reactivity of slum children by helminthic infection.

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.

Possible relationship between allergic disease and infection by Giardia lamblia.

In order to better understand the possible relationship between allergic reactivity and infection with G. lamblia, specific IgE responses and skin test reactivity were evaluated in allergic or nonallergic Venezuelan children, with or without G. lamblia infection. Two groups of children were studied: one from our Allergy Clinic and the other from a slum area of Caracas. The total serum IgE levels in children from the slum area were significantly higher in those with intestinal helminthic parasites and giardiasis, compared with those with helminthiasis only (P < .001). In atopic children with giardiasis we also found an enhanced IgE antibody response to common environmental allergens (P < .05). As G. lamblia produces intestinal mucosal damage, we also studied the reactivity to cow milk and found that 22% of the children belonging to the low socioeconomic level demonstrated the presence of significant levels of specific IgE against this antigen. Of these milk-positive subjects, 40% were infected by G. lamblia in contrast to only 21% of the milk-negative children (P < .05). These results suggest that children with giardiasis may be exposed to greater amounts of intestinally absorbed antigens. We also studied the specific allergic response to G. lamblia, and found that in an unselected group of children of low socioeconomic level, 25% had positive skin tests, as did 50% of persons with symptomatic giardiasis. The presence of serum anti-Giardia IgE was also demonstrated in 22% of patients with giardiasis.

Effect of age and helminthic infection on IgE levels in slum children.

Helminthic infections can cause an IL-4-dependent polyclonal synthesis of IgE, which is the major cause of the elevated serum levels of this immunoglobulin in tropical populations. In the present study, we measured the IgE levels in the serum of children of different ages in slum areas of Caracas, Venezuela, where intestinal helminths are endemic. As would be expected, in children over 5 years of age, the IgE levels were highly elevated, and in addition, the cord blood serum levels were higher than those reported for populations where parasitic infections are uncommon. However, the IgE levels measured in the sera of children under 5 years of age were relatively low, and within the generally accepted normal ranges. This was surprising because the latter children were infected by parasites and had high IgG antibody levels against helminths. We found, however, that whereas older children had detectable IL-4 levels in their sera, the younger children did not. These results suggest that, despite infection of these slum children by common intestinal helminths, a polyclonal stimulation of IgE synthesis did not occur, possibly due to a lack of IL-4 production by an immature immune system.

Relationship between the degree of poverty and the IgE response to Ascaris infection in slum children.

We examined a group of urban slum children in Caracas, Venezuela, and demonstrated the relationship that exists between poverty, conditions of hygiene and the prevalence of helminth infection. Concordant with the high prevalence of helminth infection in these children, the total serum levels of immunoglobulin E (IgE) and blood eosinophilia were elevated and were directly related to the degree of poverty and lack of sanitary facilities. However, in contrast, the reverse pattern was observed for the specific allergic response to these parasites. Thus, the immediate hypersensitivity skin test reactivity to Ascaris antigens, and the serum levels of specific anti-Ascaris IgE antibody, were lowest in the poorest children, who had the highest prevalence of helminth infection and the highest total IgE levels. As allergic-type reactions may participate in protective mechanisms against helminths, these results suggest that poverty and poor sanitary conditions may, by influencing the IgE response, compromise the resistance of such children to parasitic infections.

Allergic reactivity of children of different socioeconomic levels in tropical populations.

Widely variable prevalences of allergic diseases have been reported in tropical populations, and this has been suggested to be due to effects of the nonspecific polyclonal stimulation of IgE synthesis caused by the helminthic infections that are endemic in these areas. Since 1980, we have been evaluating the allergic reactivity of different socioeconomic sectors of the population of tropical Venezuela (lat. 2-12 degrees N), and in the present study analyze the overall results obtained in the laboratory evaluation of children (5-15 years of age) belonging to these groups. Children of medium-high socioeconomic level (M-HSEL), who experience occasional helminthic infections, have moderately high total serum IgE levels, and have elevated skin test positivities and specific IgE levels against environmental allergens. Persons of low socioeconomic level, in the urban, and particularly rural situation experience frequent helminthic infection, and have highly elevated total serum IgE levels. In contrast to the M-HSEL, the majority of these children have detectable specific IgE antibody against a variety of inhalant allergens, but relatively few have high levels, and their skin test positivity is also low. In these frequently parasitized persons, evidence of saturation of mast cell Fc epsilon receptors was found by tests of passive sensitization. We propose, therefore, that helminthic parasites have a biphasic effect on allergic reactivity; occasional infections are stimulatory, via their nonspecific potentiation of IgE synthesis against environmental allergens, and frequent infections are suppressive due to the widely polyclonal stimulation that they cause, resulting in both diminished specific antibody production against any given allergen and mast cell Fc epsilon receptor saturation.