Differences in both prevalence and titre of specific immunoglobulin E among children with asthma in affluent and poor communities within a large town in Ghana.

Background Reports from several African countries have noted an increasing prevalence of asthma in areas of extensive urbanization. Objective To investigate the relevance of allergen-specific sensitization and body mass index (BMI) to asthma/wheezing and exercise-induced bronchospasm (EIB) among children from affluent and poorer communities within a large town in Ghana. Methods Children with physician-diagnosed asthma and/or current wheezing aged 9-16 years (n=99; cases) from three schools with differing socio-economic backgrounds [urban affluent (UA), urban poor (UP) or suburban/rural (SR)] were recruited from a cross-sectional study (n=1848) in Kumasi, Ghana, and matched according to age, sex and area of residence with non-asthmatic/non-wheezy controls. We assayed sera for IgE antibodies to mite, cat, dog, cockroach, Ascaris and galactose-α-1,3-galactose. Results Children from the UA school had the lowest total serum IgE. However, cases from the UA school had a higher prevalence and mean titre of sIgE to mite (71.4%, 21.2IU/mL) when compared with controls (14.3%, 0.8IU/mL) or cases from UP (30%, 0.8IU/mL) and SR community (47.8%, 1.6IU/mL). While similar findings were observed with EIB in the whole population, among cases there was no difference in IgE antibody prevalence or titre between children with or without EIB. BMI was higher among UA children with and without asthma; in UP and SR communities, children with EIB (n=14) had a significantly higher BMI compared with children with asthma/wheezing without EIB (n=38) (18.2 vs. 16.4, respectively, P<0.01). Conclusions and Clinical Relevance In the relatively affluent school, asthma/wheezing and EIB were associated with high titre IgE antibodies to mite, decreased total IgE, and increased BMI. This contrasted with children in the urban poor school and suggests that changes relevant to a Western model of childhood asthma can occur within a short geographical distance within a large city in Africa. © 2011 Blackwell Publishing Ltd

House dust mite reduction and avoidance measures for treating eczema

BACKGROUND: Eczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can relapse and remit over time. As many as a third of people with eczema who have a positive test for allergy to house dust mite have reported worsening of eczema or respiratory symptoms when exposed to dust. OBJECTIVES: To assess the effects of all house dust mite reduction and avoidance measures for the treatment of eczema. SEARCH METHODS: We searched the following databases up to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant studies. We handsearched abstracts from international eczema and allergy meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any of the house dust mite reduction and avoidance measures for the treatment of eczema, which included participants of any age diagnosed by a clinician with eczema as defined by the World Allergy Organization. We included all non‐pharmacological and pharmacological interventions that sought to reduce or avoid exposure to house dust mite and their allergenic faeces. The comparators were any active treatment, no treatment, placebo, or standard care only. DATA COLLECTION AND ANALYSIS: Two authors independently checked the titles and abstracts identified, and there were no disagreements. We contacted authors of included studies for additional information. We assessed the risk of bias using Cochrane methodology. MAIN RESULTS: We included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high‐quality vacuuming of carpets and mattresses, and sprays that kill house dust mites. Four studies assessed our first primary outcome of 'Clinician‐assessed eczema severity using a named scale'. Of these, one study (n = 20) did not show any significant short‐term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high‐filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low‐filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups. With regard to the secondary outcomes 'Participant‐ or caregiver‐assessed global eczema severity score' and the 'Amount and frequency of topical treatment required', one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed 'Sensitivity to house dust mite allergen using a marker'; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials. None of the seven included studies assessed our second primary outcome 'Participant‐ or caregiver‐assessed eczema‐related quality of life using a named instrument' or the secondary outcome of 'Adverse effects'. We were unable to combine any of our results because of variability in the interventions and paucity of data. AUTHORS' CONCLUSIONS: We were unable to determine clear implications to inform clinical practice from the very low‐quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High‐quality long‐term trials of single, easy‐to‐administer house dust mite reduction or avoidance measures are worth pursuing

A Modern-Day Purgatory: Older Emergency Department Patients with Non-Operative Injuries

Older adults frequently present to the emergency department (ED) with injuries that do not require operative treatment but are sufficiently severe to make it unsafe for them to return home. These patients typically do not meet criteria for an ‘inpatient’ hospital admission. However, because of the limited reimbursement for observation patients, admitting physicians are often reluctant to accept these patients in to observation. Admission to a skilled nursing or assisted living facility from the ED or rapid access to additional in-home care is also often difficult or impossible. As a result, older patients with non-operative injuries often spend a long time in the ED waiting for an appropriate disposition. We describe the challenges of identifying an appropriate disposition for these patients, the consequences for patients, and some potential solutions to this commonly encountered problem

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Determinants and impact of giardia infection in the first 2 years of life in the MAL-ED birth cohort

Background: Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study.Methods: From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression.Results: The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years.Conclusion: Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestina

Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: A reanalysis of the MAL-ED cohort study

Background: Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study.Methods: We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0–2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics.Findings: We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6–71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8–38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6–39·5) was more common than bacterial (25·0%, 23·4–28·4) and parasitic diarrhoea (3·5%, 3·0–5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8–29·9), sapovirus (22·8, 18·9–27·5), rotavirus (20·7, 18·8–23·0), adenovirus 40/41 (19·0, 16·8–23·0), enterotoxigenic Escherichia coli (18·8, 16·5–23·8), norovirus (15·4, 13·5–20·1), astrovirus (15·0, 12·0–19·5), Campylobacter jejuni or C coli (12·1, 8·5–17·2), Cryptosporidium (5·8, 4·3–8·3), and typical enteropathogenic E coli (5·4, 2·8–9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% [95% CI 46·7–54·1], specificity 84·0% [83·0–84·9]) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% [95% CI 12·1–17·3], specificity 96·5% [96·0–97·0]).Interpretation: Quantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings

Use of antibiotics in children younger than two years in eight countries: A prospective cohort study

Objective: To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics.Methods: Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class.Findings: Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites.Conclusion: Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest

Serum IgE Reactivity Profiling in an Asthma Affected Cohort

BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile