Adenovirus species C is associated with chronic suppurative lung diseases in children

Background The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV+). Presence of bacterial infection (defined as ≥104 colony-forming units/mL) was compared between BAL HAdV+ and HAdV negative (HAdV−) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results Species C HAdVs were identified in 23 of 24 (96%) HAdV+ children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV+ BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV+. Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV+ of the lower airways and influences the likelihood of bacterial coinfection

Intravitreal drug delivery in retinal disease : are we out of our depth?

Introduction With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise. Areas covered We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally. Expert opinion Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully; however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.

Macular retinal layer thickness in childhood

Purpose To examine macular retinal thickness and retinal layer thickness with spectral domain optical coherence tomography (OCT) in a population of children with normal ocular health and minimal refractive errors. Methods High resolution macular OCT scans from 196 children aged from 4 to 12 years (mean age 8 ± 2 years) were analysed to determine total retinal thickness and the thickness of 6 different retinal layers across the central 5 mm of the posterior pole. Automated segmentation with manual correction was used to derive retinal thickness values. Results The mean total retinal thickness in the central 1 mm foveal zone was 255 ± 16 μm, and this increased significantly with age (mean increase of 1.8 microns per year) in childhood (p<0.001). Age-related increases in thickness of some retinal layers were also observed, with changes of highest statistical significance found in the outer retinal layers in the central foveal region (p<0.01). Significant topographical variations in thickness of each of the retinal layers were also observed (p<0.001). Conclusions Small magnitude, statistically significant increases in total retinal thickness and retinal layer thickness occur from early childhood to adolescence. The most prominent changes appear to occur in the outer retinal layers of the central fovea.

Is retinal shape different in Asians and Caucasians? Estimation from peripheral refraction and peripheral eye length methods

Purpose:Race appears to be associated with myopiogenesis, with East Asians showing high myopia prevalence. Considering structural variations in the eye, it is possible that retinal shapes are different between races. The purpose of this study was to quantify and compare retinal shapes between racial groups using peripheral refraction (PR) and peripheral eye lengths (PEL). Methods:A Shin-Nippon SRW5000 autorefractor and a Haag-Streit Lenstar LS900 biometer measured PR and PEL, respectively, along horizontal (H) and vertical (V) fields out to ±35° in 5° steps in 29 Caucasian (CA), 16 South Asian (SA) and 23 East Asian (EA) young adults (spherical equivalent range +0.75D to –5.00D in all groups). Retinal vertex curvature Rv and asphericity Q were determined from two methods: a) PR (Dunne): The Gullstrand-Emsley eye was modified according to participant’s intraocular lengths and anterior cornea curvature. Ray-tracing was performed at each angle through the stop, altering cornea asphericity until peripheral astigmatism matched experimental measurements. Retinal curvature and hence retinal co-ordinate intersection with the chief ray were altered until sagittal refraction matched its measurement. b) PEL: Ray-tracing was performed at each angle through the anterior corneal centre of curvature of the Gullstrand-Emsley eye. Ignoring lens refraction, retinal co-ordinates relative to the fovea were determined from PEL and trigonometry. From sets of retinal co-ordinates, conic retinal shapes were fitted in terms of Rv and Q. Repeated-measures ANOVA were conducted on Rv and Q, and post hoc t-tests with Bonferroni correction were used to compare races. Results:In all racial groups both methods showed greater Rv for the horizontal than for the vertical meridian and greater Rv for myopes than emmetropes. Rv was greater in EA than in CA (P=0.02), with Rv for SA being intermediate and not significantly different from CA and EA. The PEL method provided larger Rv than the PR method: PEL: EA vs CA 87±13 vs 83±11 m-1 (H), 79±13 vs 72±14 m-1 (V); PR: EA vs CA 79±10 vs 67±10 m-1 (H), 71±17 vs 66±12 m-1 (V). Q did not vary significantly with race. Conclusions:Estimates of Rv, but not of Q, varied significantly with race. The greater Rv found in EA than in CA and the comparatively high prevalence rate of myopia in many Asian countries may be related.

Retinal anatomy of the New Zealand kiwi: Structural traits consistent with their nocturnal behavior

Kiwi (Apteryx spp.) have a visual system unlike that of other nocturnal birds, and have specializations to their auditory, olfactory and tactile systems. Eye size, binocular visual fields and visual brain centers in kiwi are proportionally the smallest yet recorded among birds. Given the many unique features of the kiwi visual system, we examined the laminar organization of the kiwi retina to determine if they evolved increased light sensitivity with a shift to a nocturnal niche or if they retained features of their diurnal ancestor. The laminar organization of the kiwi retina was consistent with an ability to detect low light levels similar to that of other nocturnal species. In particular, the retina appeared to have a high proportion of rod photoreceptors compared to diurnal species, as evidenced by a thick outer nuclear layer, and also numerous thin photoreceptor segments intercalated among the conical shaped cone photoreceptor inner segments. Therefore, the retinal structure of kiwi was consistent with increased light sensitivity, although other features of the visual system, such as eye size, suggest a reduced reliance on vision. The unique combination of a nocturnal retina and smaller than expected eye size, binocular visual fields and brain regions make the kiwi visual system unlike that of any bird examined to date. Whether these features of their visual system are an evolutionary design that meets their specific visual needs or are a remnant of a kiwi ancestor that relied more heavily on vision is yet to be determined.

Retinal tissue thickness is reduced in diabetic peripheral neuropathy

Aim Retinal tissue integrity in relation to diabetic neuropathy is not known. The aim of this study was to investigate retinal tissue thickness in relation to diabetic peripheral neuropathy (DPN) with and without diabetic retinopathy (DR). Methods Full retinal thickness at the parafoveal and perifoveal macula and neuro-retinal thickness around the optic nerve head (ONH) and at the macula was examined using spectral domain optical coherence tomography. The eye on the hand-dominant side of 85 individuals with type 1 diabetes and 66 individuals with type 2 diabetes, with or without DR and DPN, were compared to the eyes (n=45) of age-matched non-diabetic controls. Diabetic neuropathy was defined as Neuropathy Disability Score (NDS) ≥3 on a scale of 0-10. A general linear model was used to examine the relationship between diabetic neuropathy and foveal, parafoveal and perifoveal retinal thickness and neuro-retinal thickness, in relation to DR status, age, gender, HbA1c levels and duration of diabetes. A p-value of <0.05 was considered statistically significant. Results Perifoveal retinal thickness is reduced with increasing severity of neuropathy, especially in the inferior hemisphere (p=0.004); this effect was not related to age (p=0.088). For every unit increase in NDS score, the inferior perifoveal retinal thickness reduced by 1.64 μm. Neuro-retinal thickness around the ONH decreased with increasing severity of neuropathy (p<0.014 for average and hemisphere thicknesses); for every unit increase in NDS, neuro-retinal thickness around the ONH reduced by 1.23 μm. Retinal thickness in the parafovea was increased in the absence of DR (p<0.017 for average and hemisphere thicknesses). Neuro-retinal thickness at the macula was inversely related to age alone (p<0.001). All retinal parameters, except the inferior perifovea, reduced with advancing age (p<0.007 for all). Conclusions Diabetic neuropathy is associated with changes in full retinal thickness and neuro-retinal layers. This may represent a second threat to vision integrity, in addition to the better-characterised retinopathy. This study provides new knowledge about the anatomical aspects of the retinal tissue in relation to neuropathy and retinopathy.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010

BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Environmental exposures : an underrecognized contribution to noncommunicable diseases

Previous attempts to determine the degree to which exposure to environmental factors contribute to noncommunicable diseases (NCDs) have been very conservative and have significantly underestimated the actual contribution of the environment for at least two reasons. Firstly, most previous reports have excluded the contribution of lifestyle behavioral risk factors, but these usually involve significant exposure to environmental chemicals that increase risk of disease. Secondly, early life exposure to chemical contaminants is now clearly associated with an elevated risk of several diseases later in life, but these connections are often difficult to discern. This is especially true for asthma and neurodevelopmental conditions, but there is also a major contribution to the development of obesity and chronic diseases. Most cancers are caused by environmental exposures in genetically susceptible individuals. In addition, new information shows significant associations between cardiovascular diseases and diabetes and exposure to environmental chemicals present in air, food, and water. These relationships likely reflect the combination of epigenetic effects and gene induction. Environmental factors contribute significantly more to NCDs than previous reports have suggested. Prevention needs to shift focus from individual responsibility to societal responsibility and an understanding that effective prevention of NCDs ultimately relies on improved environmental management to reduce exposure to modifiable risks.

Poverty and non-communicable diseases in South Africa

Background: High levels of wealth inequality with improved health statistics in South Africa (SA) provide an important opportunity to investigate non-communicable diseases (NCDs) among the poor. Aims: This paper uses two distinct national data sets to contrast patterns of mortality in rich and poor areas and explore the associations between poverty, risk factors, health care and selected NCDs diseases in South African adults. Methods: Causes of premature mortality in 1996 experienced in the poorest magisterial districts are compared with those in the richest, using average household wealth to classify districts. Logistic and multinomial regression are used to investigate the association of a household asset index and selected chronic conditions, related risk factors and healthcare indicators using data from the 1998 South African Demographic and Health Survey. Results: NCDs accounted for 39% and 33% of premature mortality in rich and poor districts respectively. The household survey data showed that the risk factors hypertension and obesity increased with increasing wealth, while most of the lifestyle factors, such as light smoking, domestic exposure to ``smoky'' fuels and alcohol dependence were associated with poverty. Treatment status for hypertension and asthma was worse for poor people than for rich people. Conclusions: The study suggests that NCDs and lifestyle-related risk factors are prevalent among the poor in SA and treatment for chronic diseases is lacking for poor people. The observed increase in hypertension and obesity with wealth suggests that unless comprehensive health promotion strategies are implemented, there will be an unmanageable chronic disease epidemic with future socioeconomic development in SA.

Use of partial coherence interferometry in measuring retinal shape

This study concerned development and validation of a simple and inexpensive method involving partial coherence interferometry for measuring retinal shape, and its use in exploring association between retinal shape and myopia. Retinal shapes estimates using partial coherence interferometry were validated against estimates obtained from magnetic resonance imaging. Steeper retinas were found along the horizontal than along the vertical meridian, in myopes than in emmetropes, and in East Asian myopes than in Caucasian myopes. The racial differences, combined with the high prevalence of myopia in East Asia, suggest that retinal shape may play a role in myopia development.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases

The potential impact of climate change and ultraviolet radiation on vaccine preventable infectious diseases and immunisation service delivery system

Climate change and solar ultraviolet radiation may affect vaccine-preventable infectious diseases (VPID), the human immune response process and the immunization service delivery system. We systematically reviewed the scientific literature and identified 37 relevant publications. Our study shows that climate variability and ultraviolet radiation may potentially affect VPID and the immunization delivery system through modulating vector reproduction and vaccination effectiveness, possibly influencing human immune response systems to the vaccination, and disturbing immunization service delivery. Further research is needed to determine these affects on climate-sensitive VPID and on human immune response to common vaccines. Such research will facilitate the development and delivery of optimal vaccination programs for target populations, to meet the goal of disease control and elimination.

Role of big data in the early detection of Ebola and other emerging infectious diseases

The lack of adequate disease surveillance systems in Ebola-affected areas has both reduced the ability to respond locally and has increased global risk. There is a need to improve disease surveillance in vulnerable regions, and digital surveillance could present a viable approach.