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Biomedical subjects

I Hagel

Publications and source records attributed to I Hagel.

At least 19 recordsLinked to original sources

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.

Adult↗

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.

Analysis of Variance↗

[Influence of helminthic infections and nutritional status on immune response in Venezuelan children].

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.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

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.

Anthelmintics↗

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.

Antibodies, Protozoan↗

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.

Adolescent↗

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.

Adolescent↗

Comparable seropositivity for ascariasis and toxocariasis in tropical slum children.

The seropositivities for infection by Ascaris lumbricoides and Toxocara canis were determined in children (1-15 years old) of a slum area of Caracas, Venezuela, and the levels that indicate the presence of active infection were defined. In children aged from 1 to 3 years, approximately 10% were positive for either parasite, and this figure increased to about 30% in 4- to 6-year-olds. For toxocariasis, the percentage of positivity remained at this level up to the age of 15 years. Whilst the positivity in children 10-15 years of age was comparable for Ascaris and Toxocara, a peak of positivity (50%) was found for Ascaris at 7-9 years of age. These results indicate that for these urban slum children, infection by Toxocara is essentially as common as that by Ascaris and, thus, that toxocariasis represents a potential public health problem in the tropical environment that is largely overlooked.

Adolescent↗

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.

Adolescent↗

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.

Animals↗

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.

Allergens↗

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.

Adolescent↗

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.

Animals↗

Bronchoconstriction in helminthic infection.

In order to determine whether infection by helminthic parasites can be associated with a state of bronchoconstriction, we evaluated the response to the inhalation of a bronchodilator before and after long-term anthelmintic treatment of children in a urban slum of Caracas, Venezuela. In untreated children, a direct association was found between the degree of helminthic infection and the increase in peak expiratory flow rates caused by the bronchodilator. The elimination of the infections was accompanied by a significant decrease in response to the bronchodilator. These results indicate that helminthic infection could contribute to the development of asthmatic conditions in areas where these parasites are endemic.

Albuterol↗