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Background: There are limited data from non‐industrialized settings on the effects of early life viral respiratory disease on childhood respiratory illness. We followed a birth cohort in tropical Ecuador to understand how early viral respiratory disease, in the context of exposures affecting airway inflammation including ascariasis, affect wheezing illness, asthma, and rhinoconjunctivitis in later childhood. Methods: A surveillance cohort nested within a birth cohort was monitored for respiratory infections during the first 2 years in rural Ecuador and followed for 8 years for the development of wheeze and rhinoconjunctivitis. Nasal swabs were examined for viruses by polymerase chain reaction and respiratory symptom data on recent wheeze and rhinoconjunctivitis were collected by periodic questionnaires at 3, 5, and 8 years. Stools from pregnant mothers and periodically from children aged 2 years were examined microscopically for soil‐transmitted helminths. Atopy was measured by allergen skin prick testing at 2 years. Spirometry, fractional exhaled nitric oxide measurement, and nasal washes were performed at 8 years. Associations between clinically significant respiratory disease (CSRD) and wheezing or rhinoconjunctivitis at 3, 5, and 8 years were estimated using multivariable logistic regression. Results: Four hundred and twenty six children were followed of which 67.7% had at least one CSRD episode; 12% had respiratory syncytial virus (RSV)+CSRD and 36% had rhinovirus (RHV)+CSRD. All‐cause CSRD was associated with increased wheeze at 3 (OR 2.33 [95% confidence intervals (CI) 1.23–4.40]) and 5 (OR: 2.12 [95% CI 1.12–4.01]) years. RHV+CSRD was more strongly associated with wheeze at 3 years in STH‐infected (STH‐infected [OR 13.41, 95% CI 1.56–115.64] vs. uninfected [OR 1.68, 95% CI 0.73–3.84]) and SPT+ (SPT+ [OR 9.42, 95% CI 1.88–47.15] versus SPT‐ [OR 1.92, 95% CI 0.84–4.38]) children. No associations were observed between CSRD and rhinoconjunctivitis. Discussion: CSRD was significantly associated with childhood wheeze with stronger associations observed for RHV+CSRD in SPT+ and STH‐infected children. [ABSTRACT FROM AUTHOR]

Background Despite the high asthma rates described in Latin America, asthma risk factors in poor urban settings are not well established. We investigated risk factors for acute asthma among Ecuadorian children. Methods A matched case-control study was carried out in a public hospital serving a coastal city. Children with acute asthma were age- and sex-matched to non-asthmatics. A questionnaire was administered, and blood, as well as stool, and nasopharyngeal swabs were collected. Results Sixty cases and 119 controls aged 5-15 were evaluated. High proportions of cases were atopic with population-attributable fractions for atopy of 68.5% for sIgE and 57.2% for SPT. Acute asthma risk increased with greater titers of mite IgE (3.51-50 kU/l vs. <0.70kU/l - OR 4.56, 95% CI 1.48-14.06, p = 0.008; >50kU/l vs. <0.70kU/l - OR 41.98, 95% CI: 8.97-196.39, p < 0.001). Asthma risk was significantly independently associated with bronchiolitis (adj. OR: 38.9, 95% CI 3.26-465), parental educational level (adj. OR 1.26, 95% CI: 1.08-1.46), and presence of sIgE (adj. OR: 36.7, 95% CI: 4.00-337), while a reduced risk was associated with current contact with pets (adj. OR: 0.07, 95% CI: 0.01-0.56). Rhinovirus infection was more frequent in cases (cases 35.6% vs. controls 7.8%, p = 0.002). None of the cases were on maintenance therapy with inhaled corticosteroids and most relied on emergency department for control. Conclusions A high proportion of children presenting to a public hospital with acute asthma were allergic to mite, particularly at high IgE titer. Poor asthma control resulted in overuse of emergency care. [ABSTRACT FROM AUTHOR]

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 schoolchildren 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin stimulated peripheral blood mononuclear cells expressing IFN-γ before and after vaccination. Vaccinated children had active ascariasis (n = 20) or had been infected but received short- (n = 13) or long-term (n = 15) repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of post-vaccination IFN-γ responses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis. [ABSTRACT FROM AUTHOR]

Background Studies conducted in transitional communities from Africa and Asia have pointed to the process of urbanisation as being responsible for the increase in asthma prevalence in developing regions. In Latin America, there are few published data available on the potential impact of urbanisation on asthma prevalence. The aim of the present study was to explore how the process of urbanisation may explain differences in asthma prevalence in transitional communities in north-eastern Ecuador. Methodology/principal findings An ecological study was conducted in 59 communities in Esmeraldas Province, Ecuador. Indicators of urbanisation were grouped into three indices representing the processes associated with urbanisation: socioeconomic, lifestyle and urban infrastructure. Categorical principal components analysis was used to generate scores for each index and a fourth index--a summary urbanisation index--was derived from the most representative variables in each of the three indices. The authors analysed the associations between community asthma prevalence and the indices, as well as with each indicator variable of every group. The overall prevalence of asthma was 10.1% (range 0-31.4% between communities). Three of the four indices presented significant associations with community asthma prevalence: socioeconomic (r=0.295, p=0.023), lifestyle (r=0.342, p=0.008) and summary urbanisation index (r=0.355, p=0.006). Variables reflecting better socioeconomic status and a more urban lifestyle were associated with greater asthma prevalence. Conclusions These data provide evidence that the prevalence of asthma increases with increasing levels of urbanisation in transitional communities, and factors associated with greater socioeconomic level and changes towards a more urban lifestyle may be particularly important. [ABSTRACT FROM AUTHOR]

Background Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. Methods A cross-sectional study was conducted among 3960 children aged 6e16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. Results A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/ day)) but inversely associated with age and birth order. Conclusions The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze. [ABSTRACT FROM AUTHOR]

Summary: There is considerable interest as to potential protective effects of soil‐transmitted helminths (STH) against allergy and allergic diseases. Here, we discuss findings of studies done of the effects of STH parasites on atopy and allergic diseases in Ecuador. While cross‐sectional studies have consistently shown a reduced prevalence of allergen skin prick test (SPT) reactivity among infected schoolchildren, the removal of these infections by repeated deworming did not affect SPT prevalence over the short‐term (ie, 12 months) but may have increased SPT prevalence over the long‐term (ie, 15‐17 years). In the case of allergic symptoms, cross‐sectional studies have generally not shown associations with STH and intervention studies showed no impact on prevalence. However, a birth cohort suggested that early STH infections might reduce wheeze by 5 years. Allergic sensitization to Ascaris, however, explained a significant proportion of wheezing among rural schoolchildren. Studies of the effects of STH on immune and inflammatory responses indicated a potential role of STH in contributing to more robust regulation. The effects of STH on allergy are likely to be determined by history of exposure over the life‐course and by interactions with a wide variety of other infectious and non‐infectious factors. [ABSTRACT FROM AUTHOR]

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 schoolchildren 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Bees are one of the most important creatures on Earth because of their pollination processes, which contribute to food security and ecosystem maintenance. The practice of apiculture is regarded as secondary. Nonetheless, producers find this activity appealing due to the added value of its products. Researchers have been paying attention to the genetic erosion processes of pollinators for decades. To propose a conservation plan for these insects, identification studies from individuals from those locations must be carried out in the same way because different environmental conditions promote individuals with distinct characteristics that are harder to see with the naked eye. A total of 45 Apis mellifera colonies were sampled from nine centers for rearing queens in the Camagüey province, Cuba. Wing geometric morphometric analysis was used to determine the ancestry and identify Africanization processes at different altitudes in managed honeybee populations on the island. A total of 350 reference wings were obtained from the pure subspecies: Apis mellifera mellifera, Apis mellifera carnica, Apis mellifera ligustica, Apis mellifera caucasia, Apis mellifera iberiensis, Apis mellifera intermissa, and Apis mellifera scutellata for the study. Our results showed that altitude influences wing shape; and that 96.0% (432) of the individuals were classified as Cuban hybrids, with a tendency to the formation of a new morphotype. In addition, a great similarity was found with the subspecies Apis mellifera mellifera, and it was confirmed that there is no Africanization due to the low presence of 0.44% (2) of this morphotype in the population under study. The greatest Mahalanobis distances were obtained for the comparisons between the center rearing of queens in the Camagüey province with the subspecies A. m. scutellata (D2 = 5.18); A. m. caucasia (D2 = 6.08); A. m. ligustica (D2 = 6.27); and A. m. carnica (D2 = 6.62). The well-defined pattern of wing shape produced by honeybee populations in Camagüey's centers for queen rearing suggests a Cuban hybrid. Moreover, it is essential to note that the populations of bees under investigation lack Africanized morphotypes, indicating that Camagüey bees have not interacted with the African lineage. [ABSTRACT FROM AUTHOR]

Asthma is an important health concern in Latin America (LA) where it is associated with variable prevalence and disease burden between countries. High prevalence and morbidity have been observed in some regions, particularly marginalized urban populations. Research over the past 10 years from LA has shown that childhood disease is primarily non‐atopic. The attenuation of atopy may be explained by enhanced immune regulation induced by intense exposures to environmental factors such as childhood infections and poor environmental conditions of the urban poor. Non‐atopic symptoms are associated with environmental and lifestyle factors including poor living conditions, respiratory infections, psychosocial stress, obesity, and a diet of highly processed foods. Ancestry (particularly African) and genetic factors increase asthma risk, and some of these factors may be specific to LA settings. Asthma in LA tends to be poorly controlled and depends on access to health care and medications. There is a need to improve management and access to medication through primary health care. Future research should consider the heterogeneity of asthma to identify relevant endotypes and underlying causes. The outcome of such research will need to focus on implementable strategies relevant to populations living in resource‐poor settings where the disease burden is greatest. [ABSTRACT FROM AUTHOR]

Background: There are few prospective longitudinal studies of soil-transmitted helminth (STH) infections during early childhood. We studied the epidemiology of and risk factors for soil-transmitted helminth infections from birth to 8 years of age in tropical Ecuador. Methods: 2,404 newborns were followed to 8 years of age with periodic stool sample collections. Stool samples were collected also from household members at the time of the child's birth and examined by microscopy. Data on social, environmental, and demographic characteristics were collected by maternal questionnaire. Associations between potential risk factors and STH infections were estimated using generalized estimated equations applied to longitudinal binary outcomes for presence or absence of infections at collection times. Results: Of 2,404 children, 1,120 (46.6%) were infected with at least one STH infection during the first 8 years of life. The risk of A. lumbricoides (16.2%) was greatest at 3 years, while risks of any STH (25.1%) and T. trichiura (16.5%) peaked at 5 years. Factors significantly associated with any STH infection in multivariable analyses included age, day-care (OR 1.34, 95% CI 1.03–1.73), maternal Afro-Ecuadorian ethnicity (non-Afro vs. Afro, OR 0.55, 95% CI 0.43–0.70) and lower educational level (secondary vs. illiterate, OR 0.31, 95% CI 0.22–0.45)), household overcrowding (OR 1.53, 95% CI 1.21–1.94)), having a latrine rather than a water closet (WC vs. latrine, OR 0.77, 95% CI 0.62–0.95)), and STH infections among household members (OR 2.03, 95% CI 1.59–2.58)). T. trichiura was more associated with poverty (high vs. low socioeconomic status, OR, 0.63, 95% CI 0.40–0.99)] and presence of infected siblings in the household (OR 3.42, 95% CI 2.24–5.22). Conclusion: STH infections, principally with A. lumbricoides and T. trichiura, peaked between 3 and 5 years in this cohort of children in tropical Ecuador. STH infections among household members were an important determinant of infection risk and could be targeted for control and elimination strategies. Author summary: Soil-transmitted helminths (STH) cause significant morbidity among children in low and middle-income countries (LMICs). We followed a birth cohort to 8 years of age in a rural area of coastal Ecuador and showed almost half acquired STH infections during childhood. The dominant STH parasites in this setting in children were Ascaris lumbricoides and Trichuris trichiura and infections peaked in frequency between 3 and 5 years of age. Risk of infection during childhood was associated with markers of marginalisation (Afro-Ecuadorian ethnicity and low educational level), household poverty (overcrowding and poor sanitation), and STH infections among other household members. There was evidence of a reduction in STH infection risk across all ages in study households over the calendar time course of this longitudinal study in parallel with improvements in living conditions, a period of economic growth, and increased government support for those living in extreme poverty. Our data indicate that targeting anthelmintic treatment at members of STH-infected households is likely to reduce the risk of infection in young children. [ABSTRACT FROM AUTHOR]

Abstract: The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6–9months, 22–26months, and 48–60months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4+ and CD8+ T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3+ T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology. [Copyright &y& Elsevier]

Summary Background Epidemiological studies have shown inverse associations between geohelminth (intestinal helminth) infection and atopy, leading to the suggestion that geohelminths might protect against allergy. Periodic deworming of school children with anthelmintics is a widely implemented intervention and has raised concerns that such programmes could increase allergy. We investigated the effect of repeated anthelmintic treatments with albendazole over 12 months on the prevalence of atopy and clinical indices of allergy. Methods We did a cluster-randomised controlled trial in schoolchildren from 68 rural schools. Children were randomly assigned by school to either albendazole (34 schools, 1164 children) every 2 months for 12 months, or to no intervention (34 schools, 1209 children). The intervention schools received a total of seven albendazole treatments. The primary outcome was atopy at 12 months (allergen skin-test reactivity), and analysis was by intention-to-treat for whole-school analyses and per protocol for children. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN61195515. Findings Data for analysis were available for all schools and from 67·4% (784 of 1164) and 70·1% (848 of 1209) of children in albendazole and no-treatment groups, respectively. Albendazole treatment caused large reductions in geohelminth prevalence over the study period (adjusted odds ratio 0·13, 95% CI 0·09-0·19, p<0·001), but there was no evidence that treatment was associated with an increase in atopy prevalence (0·97, 0·68-1·39, p=0·862), or clinical allergy (wheeze, 1·07, 0·54-2·11, p=0·848) in the albendazole compared with the no-treatment group. Interpretation We saw no increase in the prevalence of atopy or clinical allergy associated with albendazole treatment. Deworming programmes for schoolchildren are unlikely to be accompanied by an increase in allergy. [ABSTRACT FROM AUTHOR]

Background: Early‐life exposures to geohelminths may protect against development of wheeze/asthma and atopy. Objective: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years. Methods: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. Results: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite‐specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non‐atopic children. Conclusions: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086). [ABSTRACT FROM AUTHOR]

Background: Many studies have documented lower vaccine efficacy among children in low-income countries, compared with their counterparts in high-income countries. This disparity is especially apparent with respect to oral vaccines such as rotavirus and oral polio vaccines. One potential contributing factor is the presence of maternal antenatal helminth infections, which can modulate the infant's developing immune system.Methods: Using a multiplex immunoassay, we tested plasma immunoglobulin A (IgA) or immunoglobulin G (IgG) levels specific for antigens in 9 routinely administered childhood vaccines among 1639 children aged approximately 13 months enrolled in the ECUAVIDA (Ecuador Life) birth cohort study in Ecuador. We compared vaccine responses in 712 children of mothers who tested positive for helminth infections in the last trimester of pregnancy to responses in 927 children of mothers without helminth infection.Results: Plasma IgA levels specific for antigens in rotavirus vaccine and oral polio vaccine containing poliovirus serotypes 1 and 3 were all significantly higher in children of helminth-infected mothers, compared with children of uninfected mothers. Plasma IgG levels specific for diphtheria, tetanus, pertussis, measles, rubella, and Haemophilus influenzae type b vaccine antigens were comparable between the 2 groups.Conclusions: Antenatal maternal helminth infections were not associated with reduced antibody responses to infant vaccines, but rather with modestly increased IgA responses to oral vaccines. [ABSTRACT FROM AUTHOR]

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 autoimmune 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 hygiene and living conditions were associated with elevated IL-10 production within urban and rural populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies. [ABSTRACT FROM AUTHOR]

Background: Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings: Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GM-CSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance: Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases. Author Summary: Soil-transmitted helminth (STH or intestinal worm) infections are extremely common infectious diseases of childhood in developing countries. Infections tend be chronic and may last for many years. Chronic STH infections are associated with modulation of the immune response, a consequence of which may be a reduced prevalence of allergic inflammatory diseases such as asthma. The mechanisms by which STH infections suppress inflammatory responses are poorly understood. In this study, we hypothesized that STH infections may affect immune responses through alterations of immune homeostasis (or the steady-state adjustments of the immune system that maintain equilibrium). We investigated the capacity of blood from children classified as having no, light, or chronic STH infections to produce cytokines at rest (i.e. no immunologic stimulation) and the expression of genes in blood samples. Our data show that blood cells of children with chronic STH infections have an altered immune response that is likely to be associated with less allergic inflammation (the modified Th2 response) and that the expression of some inflammatory genes are reduced. Our findings provide insights into the mechanisms by which STH infections suppress immune responses in children to ensure the survival of the parasite and reduce inflammation. [ABSTRACT FROM AUTHOR]

Background: Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings: Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GMCSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance: Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Geohelminth infections are associated with modulation of immunity to parasite antigens and aeroallergens. To investigate the possibility that this modulation is affected by anthelmintic treatment, we compared cytokine responses in children who were treated with repeated doses of albendazole over 1 year versus those in children who had were not treated. Wholeblood samples were cultured with Ascaris antigen and house dust mite and cockroach allergens, and levels of interleukin (IL)-5, IL-13, interferon-γ, and IL-10 were measured. Anthelmintic treatment was associated with enhanced production of Th2cytokines in response to parasite antigen but did not affect responses to aeroallergens. The data indicate that long-term treatment may be associated with increased Th2 antiparasite immunity. [ABSTRACT FROM AUTHOR]

Background: In areas where intestinal helminth infections are endemic, infections by these parasites may protect against skin test-measured reactivity to allergens, and it has been suggested that interleukin (IL)-10 may mediate this effect. This study investigated whether IL-10 and populations of IL-10+ T cells may modulate atopy in children living in an area where intestinal helminth infections are endemic.Methods: Ecuadorian schoolchildren from rural communities were assessed for skin test-measured reactivity to Periplaneta americana allergen and Dermatophagoides pteronyssinus allergen. Blood samples were collected from 39 skin test-positive and 41 skin test-negative children, and peripheral-blood leukocytes were cultured in the presence of Ascaris lumbricoides antigen, to measure IL-10 protein and the frequency of T cell populations expressing intracellular IL-10. We also investigated whether these immunological factors affected the association between allergen-specific IgE and skin test-measured reactivity to aeroallergens.Results: There was no evidence of association between the level of A. lumbricoides-induced IL-10 protein or IL-10+ T cells and skin test-measured reactivity to allergens. The association between allergen-specific IgE and skin test-measured reactivity was not affected by the level of IL-10 protein or the frequency of IL-10+ T cells.Conclusions: The results of this study do not support the notion that IL-10 plays a role in modulating atopy in children living in a tropical area where intestinal helminth infections are endemic. [ABSTRACT FROM AUTHOR]

Background. In areas where intestinal helminth infections are endemic, infections by these parasites may protect against skin test-measured reactivity to allergens, and it has been suggested that interleukin (IL)-10 may mediate this effect. This study investigated whether IL-10 and populations of IL-10+ T cells may modulate atopy in children living in an area where intestinal helminth infections are endemic. Methods. Ecuadorian schoolchildren from rural communities were assessed for skin test-measured reactivity to Periplaneta americana allergen and Dermatophagoides pteronyssinus allergen. Blood samples were collected from 39 skin test-positive and 41 skin test-negative children, and peripheral-blood leukocytes were cultured in the presence of Ascaris lumbricoides antigen, to measure IL-10 protein and the frequency of T cell populations expressing intracellular IL-10. We also investigated whether these immunological factors affected the association between allergen-specific IgE and skin test-measured reactivity to aeroallergens. Results. There was no evidence of association between the level of A. lumbricoides-induced IL-10 protein or IL-10+ T cells and skin test-measured reactivity to allergens. The association between allergen-specific IgE and skin test-measured reactivity was not affected by the level of IL-10 protein or the frequency of IL-10+ T cells. Conclusions. The results of this study do not support the notion that IL-10 plays a role in modulating atopy in children living in a tropical area where intestinal helminth infections are endemic. [ABSTRACT FROM AUTHOR]

Background: The environmental factors that determine the elevated levels of polyclonal IgE observed in populations living in the Tropics are poorly understood but may include geohelminth infections. We investigated the association between geohelminth infections and total IgE levels in school children in rural tropical Ecuador, and assessed the effect on IgE of repeated anthelmintic treatments over a period of 12 months. The study was nested within a cluster-randomized study that randomized 68 schools to receive either 400 mg of albendazole every 2 months over a year or no treatment. We studied random samples of children completing follow-up and representing four groups stratified by the presence of geohelminth infection at baseline and treatment allocation. We measured levels of total IgE and anti-A. lumbricoides IgG (used as a measure of past and current geohelminth infectious exposure) in blood samples collected at the start of the study and after 12 months. Results: We observed elevated levels of total IgE (compared to standard reference values) at the start of the study in this population of school children (geometric mean, 1,004 IU/mL, range 12 to 22,608 IU/mL)) and baseline IgE levels were strongly associated with parameters of geohelminth infection but not with age, nutritional and socioeconomic status. After 12 months, levels of IgE fell significantly in the treatment (by 35.1%) and no treatment (by 10.4%) groups, respectively, but the fall was significantly greater in the treatment group. Falls in IgE were independently associated with albendazole treatment, having a baseline geohelminth infection and with high baseline levels of anti-A. lumbricoides IgG. Increases in IgE at 12 months were associated with the presence of geohelminth infections and increasing levels of anti-A. lumbricoides IgG at 12 months independent of treatment allocation. Conclusion: The data provide evidence that geohelminth infections are an important determinant of total IgE in school children in the rural Tropics and that periodic anthelmintic treatments over 12 months are associated with reductions in IgE. The failure of anthelmintic treatment to reduce IgE levels to that considered normal in industrialized countries may be attributed to continued exposure of children to geohelminths or to the effects of infections in early life in programming a long-lasting Th2-biassed immunity. [ABSTRACT FROM AUTHOR]