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Tel Aviv University: American Friends -- 1965-69 -- Correspondence, Individual -- letter, 1969-03-07
Letter from Cooper, Philip to Sabin, Albert B. dated 1969-03-07.Sabin Collection Fair Use Policy</a
Tel Aviv University: American Friends -- 1965-69 -- Correspondence, Individual -- letter, 1969-04-21
Letter from Cooper, Philip to Sabin, Albert B. dated 1969-04-21.Sabin Collection Fair Use Policy</a
Effect of urban vs. rural residence on the association between atopy and wheeze in Latin America: findings from a casease control analysis.
Background
The association between atopy and asthma is attenuated in non-affluent populations, an effect that may be explained by childhood infections such as geohelminths.
Objective
To investigate the association between atopy and wheeze in schoolchildren living in urban and rural areas of Ecuador and examine the effects of geohelminths on this association.
Methods
We performed nested case–control studies among comparable populations of schoolchildren living in rural communities and urban neighbourhoods in the Province of Esmeraldas, Ecuador. We detected geohelminths in stool samples, measured recent wheeze and environmental exposures by parental questionnaire, and atopy by specific IgE (sIgE) and skin prick test (SPT) reactivity to aeroallergens.
Results
Atopy, particularly sIgE to house dust mite (HDM), was more strongly associated with recent wheeze in urban than rural schoolchildren: (urban, adj. OR 5.19, 95% CI 3.37–8.00, P < 0.0001; rural, adj. OR 1.81, 95%CI 1.09–2.99, P = 0.02; interaction, P < 0.001). The population fractions of wheeze attributable to atopy were approximately two-fold greater in urban schoolchildren: SPT to any allergen (urban 23.5% vs. rural 10.1%), SPT to HDM (urban 18.5% vs. rural 9.6%), and anti-HDM IgE (urban 26.5% vs. rural 10.5%), while anti-Ascaris IgE was related to wheeze in a high proportion of rural (49.7%) and urban (35.4%) children. The association between atopy and recent wheeze was attenuated by markers of geohelminth infections.
Conclusions
Our data suggest that urban residence modifies the association between HDM atopy and recent wheeze, and this effect is explained partly by geohelminth infections.
Introduction
Atopy is a consistently strong risk factor for asthma in industrialized countries [1, 2], but this association appears to be weaker [3-6] in non-industrialized countries. A predominance of non-atopic over atopic wheeze/asthma has been observed in several Latin American countries including Brazil [3, 4, 7], Peru [8], and Ecuador [9].
The association between atopy and allergic disease appears to be stronger in affluent compared to non-affluent [6] and in urban compared to rural populations [10, 11]. Urban–rural differences in the prevalence of environmental exposures that attenuate atopy could explain these observations. Examples of environmental exposures that may suppress atopy include household pets [12], farming exposures [13, 14], and infections during childhood [15]. Geohelminth infections, that are common chronic parasitic infections of predominantly low-income rural populations in the tropics, may have a role in attenuating the association between atopy and allergic symptoms [16] including wheeze [17, 18].
The aim of this study was to investigate if associations between atopy and recent wheeze are modified by rural vs. urban residence and to explore which environmental exposures including geohelminth infections might contribute to such an effect. To do this, we conducted nested case–control studies comparing schoolchildren living in rural communities, as reported previously [17], with urban neighbourhoods in the Province of Esmeraldas in Ecuador
Lifestyle domains as determinants of wheeze prevalence in urban and rural schoolchildren in Ecuador: cross sectional analysis
Background: The acquisition of a modern lifestyle may explain variations in asthma prevalence between urban and rural areas in developing countries. However, the effects of lifestyle on asthma have been investigated as individual factors with little consideration given to the effects of lifestyle as a set of attributes. The aim of the present study was to identify modern lifestyle domains and assess how these domains might explain wheeze prevalence in urban and rural areas. Methods: We analysed data from cross-sectional studies of urban and rural choolchildren in Esmeraldas Province, Ecuador. Variables were grouped as indicators of socioeconomic factors, sedentarism, agricultural activities and household characteristics to represent the main lifestyle features of the study population. We used multiple correspondence analyses to identify common lifestyle domains and cluster analysis to allocate children to each domain. We evaluated associations between domains and recent wheeze by logistic regression. Results: We identified 2–3 lifestyle domains for each variable group. Although wheeze prevalence was similar in urban (9.4%) and rural (10.3%) schoolchildren, lifestyle domains presented clear associations with wheeze prevalence. Domains relating to home infrastructure (termed transitional, rudimentary, and basic urban) had the strongest overall effect on wheeze prevalence in both urban (rudimentary vs. basic urban, OR = 2.38, 95% CI 1.12-5.05, p = 0.024) and rural areas (transitional vs. basic urban, OR = 2.02, 95% CI 1.1-3.73, p = 0.024; rudimentary vs. basic urban, OR = 1.88, 95% CI 1.02-3.47, p = 0.043). A high level of sedentarism was associated with wheeze in the rural areas only (OR = 1.64, 95% CI 1.23-2.18, p = 0.001). Conclusions: We identified lifestyle domains associated with wheeze prevalence, particularly living in substandard housing and a high level of sedentarism. Such factors could be modified through programmes of improved housing and education. The use of lifestyle domains provides an alternative methodology for the evaluation of variations in wheeze prevalence in populations with different levels of development
Effects of maternal geohelminth infections on allergy in early childhood
Background: Maternal geohelminth infections during pregnancy may protect against allergy development in childhood. Objective:
We sought to investigate the effect of maternal geohelminths on the development of eczema, wheeze, and atopy during the first 3 years of life. Methods: A cohort of 2404 neonates was followed to 3 years of age in a rural district in coastal Ecuador. Data on wheeze and eczema were collected by means of questionnaire and physical examination at 13, 24, and 36 months of age. Atopy was measured based on skin prick test (SPT) reactivity to 9 allergens at 36 months. Maternal stool samples were examined for geohelminths by microscopy. Data on potential confounders was collected after birth by questionnaire. Results: Geohelminths were observed in 45.9% of mothers. Eczema and wheeze were reported for 17.7% and 25.9%, respectively, of 2069 (86.1%) children with complete follow-up to 3 years, and allergen SPT reactivity to any allergen was present in 17.2% and to house dust mite in 8.7%. Maternal geohelminth infections were not significantly associated with eczema (adjusted odds ratio [OR], 1.26; 95% CI, 0.98-1.61), wheeze (adjusted OR, 1.02; 95% CI, 0.82-1.27), and SPT reactivity to any allergen (adjusted OR, 0.79; 95% CI, 0.61-1.01). In subgroup analyses maternal geohelminths were associated with a significantly reduced risk of SPT reactivity to mite and other perennial allergens, and maternal ascariasis was associated with an increased risk of eczema and reduced risk of SPT reactivity to all allergens. Conclusion: Our data do not support a protective effect of maternal infections with geohelminth parasites during pregnancy against the development of eczema and wheeze in early childhood, although there was evidence in subgroup analyses for a reduction in SPT reactivity to house dust mites and perennial allergens
Effects of environment on human cytokine responses during childhood in the tropics: role of urban versus rural residence
Background: Environment may have a key role in the development of the immune system in childhood and environmental exposures associated with rural residence may explain the low prevalence of allergic and autoinmune diseases in the rural tropics. We investigated the effects of urban versus rural residence on the adaptive immune response in children living in urban and rural areas in a tropical region of Latin America. Methods: We recruited school children in either rural communities in the Province of Esmeraldas or in urban neighborhoods in the city of Esmeraldas, Ecuador. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Peripheral blood leukocytes (PBLs) in whole blood were stimulated with superantigen, parasite antigens and aeroallergens and IFN-γ, IL-5, IL-10, IL-13, and IL-17 were measured in supernatants. Results: We evaluated 440 school children; 210 living in rural communities and 230 in the city of Esmeraldas. Overall, urban children had greater access to piped water (urban 98.7 % vs. rural 1.9 %), were more likely to have a household bathroom (urban 97.4 % vs. rural 54.8 %), and were less likely to be infected with soil-transmitted helminth infections (urban 20.9 % vs. rural 73.5 %). Generally, detectable levels of cytokines were more frequent in blood from children living in urban than rural areas. Urban residence was associated with a significantly greater frequency of IL-10 production spontaneously (adjusted OR 2.56, 95 % CI 1.05-6.24) and on stimulation with Ascaris (adj. OR 2.5, 95 % CI 1.09-5.79) and house dust mite (adj. 2.24, 95 % CI 1.07-4.70) antigens. Analysis of effects of environmental exposures on SEB-induced IL-10 production within urban and rural populations showed that some environmental exposures indicative of poor hygiene (urban – higher birth order, A. lumbricoides infection; rural - no bathroom, more peri-domiciliary animals, and living in a wood/bamboo house) were associated with elevated IL-10. Conclusions: In our study population, the immune response of children living in an urban environment was associated more frequently with the production of the immune regulatory cytokine, IL-10. Some factors related to poor higiene and living conditions were associated with elevated IL-10 production within urban and rural populations
Risk Factors for Soil-Transmitted Helminth Infections during the First 3 Years of Life in the Tropics; Findings from a Birth Cohort.
Background:
Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk
factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador.
Methods and Findings:
Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by A. lumbricoides (33.2% of children) and T. trichiura (21.2%). Hookworm infection was detected in 0.9% of children. Risk of STH infection was associated with factors indicative of poverty in our study population such as Afro-Ecuadorian ethnicity and low maternal educational level. Maternal STH infections during pregnancy were strong risk factors for any childhood STH infection, infections with either A. lumbricoides or T. trichiura, and early age of first STH infection. Children of mothers with moderate to high infections intensities with A. lumbricoides were most at risk.
Conclusions:
Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children
Cohort Profile: The Ecuador Life (ECUAVIDA) study in Esmeraldas Province, Ecuador.
The ECUAVIDA birth cohort is studying the impact of exposures to soil-transmitted helminth (STH) parasites and early-life microbial exposures on the development of atopy, allergic diseases and immune responses in childhood. A total of 2404 newborns were recruited between 2006 and 2009 in a public hospital serving the rural district of Quininde, Esmeraldas Province, in a tropical region of coastal Ecuador. Detailed measurements were done around the time of the birth, at 7 and 13 months and at 2 and 3 years, and data collection is ongoing at 5 and 8 years. Data being collected include questionnaires for: sociodemographic, lifestyle, psychosocial (at 4–6 years only) and dietary (at 6–7 years only) factors; childhood morbidity and clinical outcomes; stool samples for parasites; blood samples for DNA, measurements of vaccine responses and other measures of immune function/inflammation; and anthropometrics. Allergen skin prick test reactivity is done from 2 years and measures of airway function and inflammation at 8 years
Norovirus infection and disease in an ecuadorian birth cohort: association of certain norovirus genotypes with host FUT2 secretor status
Background: Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. Methods: We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. Results: Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0–12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). Conclusions: GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children
Hygiene, atopy and wheeze - eczema - rhinitis symptoms in schoolchildren from urban and rural Ecuador.
Background:
Rural residence is protective against atopy and wheeze–rhinitis–eczema symptoms in developed countries, an effect attributed to farming and poor hygiene exposures. There are few data from developing countries addressing this question. We compared atopy and wheeze–rhinitis–eczema symptoms between urban and rural Ecuador, and explored the effects of farming and poor hygiene exposures.
Methods:
We performed cross sectional studies of schoolchildren living in rural and urban Ecuador. Data on symptoms and farming/hygiene exposures were collected by parental questionnaire, atopy by allergen skin prick test reactivity and geohelminth infections by stool examinations.
Results:
Among 2526 urban and 4295 rural schoolchildren, prevalence was: atopy (10.0% vs 12.5%, p=0.06), wheeze (9.4% vs 10.1%, p=0.05), rhinitis (8.1% vs 6.4%, p=0.02) and eczema (5.9% vs 4.7%, p=0.06). A small proportion of symptoms were attributable to atopy (range 3.9–10.7%) with greater attributable fractions for respiratory symptoms observed in urban schoolchildren. Respiratory symptoms were associated with poor hygiene/farming exposures: wheeze with lack of access to potable water; and rhinitis with household pets, no bathroom facilities and contact with large farm animals. Birth order was inversely associated with respiratory symptoms. Area of residence and atopy had few effects on these associations.
Conclusions:
Urban schoolchildren living in Ecuador have a similar prevalence of atopy, eczema and wheeze but a higher prevalence of rhinitis compared with rural children. Some farming and poor hygiene exposures were associated with an increase in the prevalence of wheeze or rhinitis while birth order was inversely associated with these symptoms
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