Understanding and controlling asthma in Latin America: A review of recent research informed by the SCAALA programme.

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.

Prospective study of factors associated with asthma attack recurrence (ATTACK) in children from three Ecuadorian cities during COVID-19: a study protocol.

INTRODUCTION: Asthma is a growing health problem in children in marginalised urban settings in low-income and middle-income countries. Asthma attacks are an important cause of emergency care attendance and long-term morbidity. We designed a prospective study, the Asthma Attacks study, to identify factors associated with recurrence of asthma attacks (or exacerbations) among children and adolescents attending emergency care in three Ecuadorian cities. METHODS AND ANALYSIS: Prospective cohort study designed to identify risk factors associated with recurrence of asthma attacks in 450 children and adolescents aged 5-17 years attending emergency care in public hospitals in three Ecuadorian cities (Quito, Cuenca and Portoviejo). The primary outcome will be rate of asthma attack recurrence during up to 12 months of follow-up. Data are being collected at baseline and during follow-up by questionnaire: sociodemographic data, asthma history and management (baseline only); recurrence of asthma symptoms and attacks (monthly); economic costs of asthma to family; Asthma Control Test; Pediatric Asthma Quality of life Questionnaire; and Newcastle Asthma Knowledge Questionnaire (baseline only). In addition, the following are being measured at baseline and during follow-up: lung function and reversibility by spirometry before and after salbutamol; fractional exhaled nitric oxide (FeNO); and presence of IgG antibodies to SARS-CoV-2 in blood. Recruitment started in 2019 but because of severe disruption to emergency services caused by the COVID-19 pandemic, eligibility criteria were modified to include asthmatic children with uncontrolled symptoms and registered with collaborating hospitals. Data will be analysed using logistic regression and survival analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Hospital General Docente de Calderon (CEISH-HGDC 2019-001) and Ecuadorian Ministry of Public Health (MSP-CGDES-2021-0041-O N° 096-2021). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy-makers, postgraduate theses, peer-review publications and a study website. Participants gave informed consent to participate in the study before taking part.

Incidence and seasonality of respiratory viruses among medically attended children with acute respiratory infections in an Ecuador birth cohort, 2011-2014.

BACKGROUND: Ecuador annually has handwashing and respiratory hygiene campaigns and seasonal influenza vaccination to prevent respiratory virus illnesses but has yet to quantify disease burden and determine epidemic timing. METHODS: To identify respiratory virus burden and assess months with epidemic activity, we followed a birth cohort in northwest Ecuador during 2011-2014. Mothers brought children to the study clinic for routine checkups at ages 1, 2, 3, 5, and 8 years or if children experienced any acute respiratory illness symptoms (e.g., cough, fever, or difficulty breathing); clinical care was provided free of charge. Those with medically attended acute respiratory infections (MAARIs) were tested for common respiratory viruses via real-time reverse-transcription polymerase chain reaction (rRT-PCR). RESULTS: In 2011, 2376 children aged 1-4 years (median 35 months) were enrolled in the respiratory cohort and monitored for 7017.5 child-years (cy). The incidence of respiratory syncytial virus (RSV) was 23.9 (95% CI 17.3-30.5), influenza 10.6 (2.4-18.8), adenoviruses 6.7 (4.6-28.0), parainfluenzas 5.0 (2.3-10.5), and rhinoviruses, bocaviruses, human metapneumoviruses, seasonal coronaviruses, and enteroviruses <3/100 cy among children aged 12-23 months and declined with age. Most (75%) influenza detections occurred April-September. CONCLUSION: Cohort children frequently had MAARIs, and while the incidence decreased rapidly among older children, more than one in five children aged 12-23 months tested positive for RSV, and one in 10 tested positive for influenza. Our findings suggest this substantial burden of influenza occurred more commonly during the winter Southern Hemisphere influenza season.

Patterns of allergic sensitization and factors associated with emergence of sensitization in the rural tropics early in the life course: findings of an Ecuadorian birth cohort.

INTRODUCTION: There are limited data on emergence of allergic sensitization (or atopy) during childhood in tropical regions. METHODS: We followed a birth cohort of 2404 newborns to 8 years in tropical Ecuador and collected: risk factor data by maternal questionnaires periodically from birth; atopy was measured by skin prick test reactivity (SPT) to aeroallergens in parents, and aeroallergens and food allergens in children at 2, 3, 5, and 8 years; and stool samples for soil-transmitted helminths (STH) from children periodically to 8 years and from parents and household members at the time of recruitment of cohort children. Data on risk factors were measured either at birth or repeatedly (time-varying) from birth to 8 years. Longitudinal repeated-measures analyses were done using generalized estimating equations to estimate an the age-dependent risk of positive SPT (SPT+) to any allergen or mite during early childhood to school age. RESULTS: SPT+ to any allergen was present in 29.0% of fathers and 24.8% of mothers, and in cohort children increased with age, initially to mite but later to cockroach, reaching 14.8% to any allergen (10.7% mite and 5.3% cockroach) at 8 years. Maternal SPT+, particularly presence of polysensitization (OR 2.04, 95% CI 1.49-2.77) significantly increased the risk of SPT+ during childhood, while household overcrowding at birth decreased the risk (OR 0.84, 95% CI 0.72-0.98). For mite sensitization, maternal polysensitization increased (OR 2.14, 95% CI 1.40-3.27) but rural residence (OR 0.69, 95% CI 0.50-0.94) and birth order (3rd -4th vs. 1st - 2nd: OR 0.71, 95% CI 0.52-0.98) decreased the risk. Time-varying exposures to agricultural activities (OR 0.77, 95% CI 0.60-0.98) and STH parasites (OR 0.70, 95% CI 0.64-0.91) during childhood decreased while anthelmintics increased the childhood risk (OR 1.47, 95% CI 1.05-2.05) of mite sensitization. CONCLUSION: Our data showed the emergence of allergic sensitization, primarily to mite and cockroach allergens, during childhood in tropical Ecuador. A role for both antenatal and postnatal factors acting as potential determinants of SPT+ emergence was observed.

The epidemiology of soil-transmitted helminth infections in children up to 8 years of age: Findings from an Ecuadorian birth cohort.

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.

Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years.

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).

α-Gal specific-IgE prevalence and levels in Ecuador and Kenya: Relation to diet, parasites, and IgG4.

BACKGROUND: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. OBJECTIVE: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. METHODS: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. RESULTS: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. CONCLUSIONS: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.

A prospective seroepidemiological study of toxocariasis during early childhood in coastal Ecuador: potential for congenital transmission and risk factors for infection.

BACKGROUND: Although Toxocara spp. infection has a worldwide distribution, to our knowledge, no data from birth cohorts have been reported in published studies on the potential for congenital transmission and determinants of infection in early childhood. METHODS: We followed 290 mother-infant pairs from birth to 5 years of age through periodic collection of data and samples at birth, 7 and 13 months and 2, 3 and 5 years of age. Data on potential risk factors and confounders were collected by maternal questionnaire. Blood for plasma was collected from the mother at time of birth and periodically from the child for detection of anti-Toxocara spp. immunoglobulin G (IgG) antibodies using a Toxocara canis larval excretory-secretory antigen-based enzyme-linked immunosorbent assay. Stool samples were collected from the mother around the time of birth and periodically from the child for microscopic detection of soil-transmitted helminths (STH). Associations between potential risk factors and Toxocara spp. seroprevalence and seroconversion were estimated using multivariable logistic regression and generalized estimating equations. RESULTS: Toxocara spp. seroprevalence was 80.7% in mothers and in children was 0%, 9.3%, 48.4%, 64.9%, and 80.9% at 7 months, 13 months, 2, 3 and 5 years, respectively. Risk factors significantly associated with increases in seroprevalence over the first 5 years of life in multivariable analyses were age [Odds ratio (OR) 2.06, 95% confidence interval (CI) 1.39-2.27, P < 0001], male sex (female vs. male: OR 0.66, 95% CI 0.48-0.89, P = 0.006), maternal ethnicity (non-Afro vs. Afro-Ecuadorian: OR 0.65, 95% CI 0.47-0.91, P = 0.011), lower maternal educational and socioeconomic level, and childhood STH (OR 2.29, 95% CI 1.51-3.47, P < 0.001). Seroconversion rates for infection were greatest at 2 years of age (3.8%/month). Factors associated significantly with seroconversion at 2, 3 or 5 years were childhood STH infection, male sex, and more frequent domestic cat exposure. CONCLUSIONS: Our data, from an area of high Toxocara spp. endemicity, indicate no congenital transmission but high rates of seroconversion after 13 months of age reaching maternal levels of seroprevalence by 5 years of age. Factors associated with seroprevalence and seroconversion included STH infections, domestic cats, maternal ethnicity, male sex, STH infections, and markers of greater poverty.

Soil-transmitted helminth parasites and allergy: Observations from Ecuador.

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.

Effect of Early-Life Geohelminth Infections on the Development of Wheezing at 5 Years of Age.

RATIONALE: Exposures to geohelminths during gestation or early childhood may reduce risk of wheezing illness/asthma and atopy during childhood in tropical regions. OBJECTIVES: To investigate the effect of maternal and early childhood geohelminths on development of wheeze/asthma and atopy during the first 5 years of life. METHODS: A cohort of 2,404 neonates was followed to 5 years of age in a rural district in coastal Ecuador. Data on wheeze were collected by questionnaire and atopy was measured by allergen skin prick test reactivity to 10 allergens at 5 years. Stool samples from mothers and children were examined for geohelminths by microscopy. MEASUREMENTS AND MAIN RESULTS: A total of 2,090 (86.9%) children were evaluated at 5 years. Geohelminths were observed in 45.5% of mothers and in 34.1% of children by 3 years. Wheeze and asthma were reported for 12.6% and 5.7% of children, respectively, whereas 14.0% had skin test reactivity at 5 years. Maternal geohelminths were associated with an increased risk of wheeze (adjusted odds ratio, 1.41; 95% confidence interval, 1.06-1.88), whereas childhood geohelminths over the first 3 years of life were associated with reduced risk of wheeze (adjusted odds ratio, 0.70; 95% confidence interval, 0.52-0.96) and asthma (adjusted odds ratio, 0.60; 95% confidence interval, 0.38-0.94) but not skin prick test reactivity. The effects on wheeze/asthma were greatest with later age of first infection, were observed only in skin test-negative children, but were not associated with parasite burden or specific geohelminths. CONCLUSIONS: Although maternal exposures to geohelminths may increase childhood wheeze, childhood geohelminths during the first 3 years may provide protection through a nonallergic mechanism. Registered as an observational study (ISRCTN41239086).

Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting.

BACKGROUND: Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. OBJECTIVE: We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. METHODS: We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. RESULTS: As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. CONCLUSIONS: Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

Rural to urban migration is associated with increased prevalence of childhood wheeze in a Latin-American city.

INTRODUCTION: The urbanisation process has been associated with increases in asthma prevalence in urban and rural areas of low-income and middle-income countries (LMICs). However, although rural to urban migration and migration between cities are considered important determinants of this process, few studies have evaluated the effects of internal migration on asthma in urban populations of LMICs. The present study evaluated the effects of internal migration on the prevalence of wheeze in an urban area of Latin America. METHODS: We did a cross-sectional analysis of 2510 schoolchildren living in the city of Esmeraldas, Ecuador. Logistic regression was used to analyse associations between childhood wheeze and different aspects of migration among schoolchildren. RESULTS: 31% of schoolchildren were migrants. Rural to urban migrants had a higher prevalence of wheeze, (adj.OR=2.01,95% CI1.30 to 3.01, p=0.001) compared with non-migrants. Age of migration and time since migration were associated with wheeze only for rural to urban migrants but not for urban to urban migrants. Children who had migrated after 3 years of age had a greater risk of wheeze (OR 2.51, 95% CI 1.56 to 3.97, p=0.001) than non-migrants while migrants with less than 5 years living in the new residence had a higher prevalence of wheeze than non-migrants (<3 years: OR=2.34, 95% CI 1.26 to 4.33, p<0.007 and 3-5 years: OR=3.03, 95% CI 1.49 to 6.15, p<0.002). CONCLUSIONS: Our study provides evidence that rural to urban migration is associated with an increase in the prevalence of wheeze among schoolchildren living in a Latin-American city. Age of migration and time since migration were important determinants of wheeze only among migrants from rural areas. A better understanding of the social and environmental effects of internal migration could improve our understanding of the causes of the increase in asthma and differences in prevalence between urban and rural populations.

Growth patterns in early childhood: Better trajectories in Afro-Ecuadorians independent of sex and socioeconomic factors.

The first years of life are the most dynamic period for childhood growth. There are limited data available on growth patterns of infants and children living in rural Latin America. The aim of this study was to describe the growth patterns from birth to 5years in children living in a rural District of tropical coastal Ecuador using data from a birth cohort of 2404 neonates. We hypothesize that there would be growth differences according to ethnicity and sex. Evaluations were conducted at birth or until 2weeks of age and at 7, 13, 24, 36 and 60months during clinic and home visits. Individual growth trajectories for weight-for-age, height-for-age and weight/height-for-age Z-scores were estimated using multilevel models. Girls were lighter and shorter than boys at birth. However, Afro-Ecuadorian children (versus mestizo or indigenous) were longer/taller and heavier throughout the first 5years of life and had greater mean trajectories for HAZ and WAZ independent of sex and socioeconomic factors. Our data indicate that ethnicity is a determinant of growth trajectories during the first 5years of life independent of socioeconomic factors in a birth cohort conducted in a rural region of Latin America.

Maternal Helminth Infection Is Associated With Higher Infant Immunoglobulin A Titers to Antigen in Orally Administered Vaccines.

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.

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 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.

A genetic analysis of Trichuris trichiura and Trichuris suis from Ecuador.

BACKGROUND: Since the nematodes Trichuris trichiura and T. suis are morphologically indistinguishable, genetic analysis is required to assess epidemiological cross-over between people and pigs. This study aimed to clarify the transmission biology of trichuriasis in Ecuador. FINDINGS: Adult Trichuris worms were collected during a parasitological survey of 132 people and 46 pigs in Esmeraldas Province, Ecuador. Morphometric analysis of 49 pig worms and 64 human worms revealed significant variation. In discriminant analysis morphometric characteristics correctly classified male worms according to host species. In PCR-RFLP analysis of the ribosomal Internal Transcribed Spacer (ITS-2) and 18S DNA (59 pig worms and 82 human worms), nearly all Trichuris exhibited expected restriction patterns. However, two pig-derived worms showed a "heterozygous-type" ITS-2 pattern, with one also having a "heterozygous-type" 18S pattern. Phylogenetic analysis of the mitochondrial large ribosomal subunit partitioned worms by host species. Notably, some Ecuadorian T. suis clustered with porcine Trichuris from USA and Denmark and some with Chinese T. suis. CONCLUSION: This is the first study in Latin America to genetically analyse Trichuris parasites. Although T. trichiura does not appear to be zoonotic in Ecuador, there is evidence of genetic exchange between T. trichiura and T. suis warranting more detailed genetic sampling.

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 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.

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.