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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]

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: 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. [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]

Summary: Ruminococcus bromii is a dominant member of the human colonic microbiota that plays a ‘keystone’ role in degrading dietary resistant starch. Recent evidence from one strain has uncovered a unique cell surface ‘amylosome’ complex that organizes starch‐degrading enzymes. New genome analysis presented here reveals further features of this complex and shows remarkable conservation of amylosome components between human colonic strains from three different continents and a R. bromii strain from the rumen of Australian cattle. These R. bromii strains encode a narrow spectrum of carbohydrate active enzymes (CAZymes) that reflect extreme specialization in starch utilization. Starch hydrolysis products are taken up mainly as oligosaccharides, with only one strain able to grow on glucose. The human strains, but not the rumen strain, also possess transporters that allow growth on galactose and fructose. R. bromii strains possess a full complement of sporulation and spore germination genes and we demonstrate the ability to form spores that survive exposure to air. Spore formation is likely to be a critical factor in the ecology of this nutritionally highly specialized bacterium, which was previously regarded as ‘non‐sporing’, helping to explain its widespread occurrence in the gut microbiota through the ability to transmit between hosts. [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]

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]

A well-tolerated oral drug is required for the treatment of mucocutaneous leishmaniasis (MCL). Current parenteral treatment regimens with pentavalent antimonials are associated with marked toxicity and significant rates of relapse.To evaluate the efficacy and tolerability of high-dose itraconazole for the treatment of MCL.An uncontrolled treatment study was performed in 13 Ecuadorian patients with MCL. Each patient received a daily dosage of 400 mg of itraconazole for a minimum of 3 months.All 13 subjects responded to itraconazole during the first month of treatment, but by 12 months after treatment the complete resolution of MCL lesions was observed in only three (23%) subjects. No adverse effects of treatment were reported. Response to treatment was associated with a short evolution of the disease and mild to moderate disease severity.Prolonged and high-dose treatment regimens with itraconazole are not effective for the treatment of the majority of patients with MCL. [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]