Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

Introduction The precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis. Methods Fieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates. Results Podoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence. Conclusions More quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients

Interpreting predictive maps of disease, highlighting the pitfalls of species distribution models in epidemiology

This is the authors' PDF version of an article published in Geospatial Health© 2014. The definitive version is available at http://geospatialhealth.netThe application of spatial modelling to epidemiology has increased significantly over the past decade, delivering enhanced understanding of the environmental and climatic factors affecting disease distributions and providing spatially continuous representations of disease risk (predictive maps). These outputs provide significant information for disease control programmes, allowing spatial targeting and tailored interventions. However, several factors (e.g. sampling protocols or temporal disease spread) can influence predictive mapping outputs. This paper proposes a conceptual framework which defines several scenarios and their potential impact on resulting predictive outputs, using simulated data to provide an exemplar. It is vital that researchers recognise these scenarios and their influence on predictive models and their outputs, as a failure to do so may lead to inaccurate interpretation of predictive maps. As long as these considerations are kept in mind, predictive mapping will continue to contribute significantly to epidemiological research and disease control planning.This work was supported by the Medical Research Council (PMA, NAW - projects G0902445 and MR/J012343/1). The funders had no role in the decision to publish or in preparation of the manuscript

La asociación : revista de primera enseñanza: Año XI Número 541 - (07/07/23)

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems

Bayesian spatial modelling and the significance of agricultural land use to scrub typhus infection in Taiwan

Scrub typhus is transmitted by the larval stage of trombiculid mites. Environmental factors, including land cover and land use, are known to influence breeding and survival of trombiculid mites and, thus, also the spatial heterogeneity of scrub typhus risk. Here, a spatially autoregressive modelling framework was applied to scrub typhus incidence data from Taiwan, covering the period 2003 to 2011, to provide increased understanding of the spatial pattern of scrub typhus risk and the environmental and socioeconomic factors contributing to this pattern. A clear spatial pattern in scrub typhus incidence was observed within Taiwan, and incidence was found to be significantly correlated with several land cover classes, temperature, elevation, normalized difference vegetation index, rainfall, population density, average income and the proportion of the population that work in agriculture. The final multivariate regression model included statistically significant correlations between scrub typhus incidence and average income (negatively correlated), the proportion of land that contained mosaics of cropland and vegetation (positively correlated) and elevation (positively correlated). These results highlight the importance of land cover on scrub typhus incidence: mosaics of cropland and vegetation represent a transitional land cover type which can provide favourable habitats for rodents and, therefore, trombiculid mites. In Taiwan, these transitional land cover areas tend to occur in less populated and mountainous areas, following the frontier establishment and subsequent partial abandonment of agricultural cultivation, due to demographic and socioeconomic changes. Future land use policy decision-making should ensure that potential public health outcomes, such as modified risk of scrub typhus, are considered

The Dispersal Ecology of Rhodesian Sleeping Sickness Following Its Introduction to a New Area

Tsetse-transmitted human and animal trypanosomiasis are constraints to both human and animal health in sub-Saharan Africa, and although these diseases have been known for over a century, there is little recent evidence demonstrating how the parasites circulate in natural hosts and ecosystems. The spread of Rhodesian sleeping sickness (caused by Trypanosoma brucei rhodesiense) within Uganda over the past 15 years has been linked to the movement of infected, untreated livestock (the predominant reservoir) from endemic areas. However, despite an understanding of the environmental dependencies of sleeping sickness, little research has focused on the environmental factors controlling transmission establishment or the spatially heterogeneous dispersal of disease following a new introduction. In the current study, an annually stratified case-control study of Rhodesian sleeping sickness cases from Serere District, Uganda was used to allow the temporal assessment of correlations between the spatial distribution of sleeping sickness and landscape factors. Significant relationships were detected between Rhodesian sleeping sickness and selected factors, including elevation and the proportion of land which was “seasonally flooding grassland” or “woodlands and dense savannah.” Temporal trends in these relationships were detected, illustrating the dispersal of Rhodesian sleeping sickness into more ‘suitable’ areas over time, with diminishing dependence on the point of introduction in concurrence with an increasing dependence on environmental and landscape factors. These results provide a novel insight into the ecology of Rhodesian sleeping sickness dispersal and may contribute towards the implementation of evidence-based control measures to prevent its further spread

Tsetse Fly (G.f. fuscipes) Distribution in the Lake Victoria Basin of Uganda

Tsetse flies transmit trypanosomes, the causative agent of human and animal African trypanosomiasis. The tsetse vector is extensively distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. Given scarce resources to carry out regular full scale field tsetse surveys to up-date existing tsetse maps, there is a need to devise inexpensive means for regularly obtaining dependable area-wide tsetse data to guide control activities. In this study we used spatial epidemiological modelling techniques (logistic regression) involving 5000 field-based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with satellite-derived environmental surrogates composed of precipitation, temperature, land cover, normalised difference vegetation index (NDVI) and elevation at the sub-national level. We used these extensive tsetse data to analyse the relationships between presence of tsetse (G. f. fuscipes) and environmental variables. The strength of the results was enhanced through the application of a spatial autologistic regression model (SARM). Using the SARM we showed that the probability of tsetse presence increased with proportion of forest cover and riverine vegetation. The key outputs are a predictive tsetse distribution map for the Lake Victoria basin of Uganda and an improved understanding of the association between tsetse presence and environmental variables. The predicted spatial distribution of tsetse in the Lake Victoria basin of Uganda will provide significant new information to assist with the spatial targeting of tsetse and trypanosomiasis control

Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Cell elongation in the grass pulvinus in response to geotropic stimulation and auxin application

Horizontally-placed segments of Avena sativa L. shoots show a negative geotropic response after a period of 30 min. This response is based on cell elongation on the lower side of the leaf-sheath base (pulvinus). Triticum aestivum L., Hordeum vulgare L. and Secale cereale L. also show geotropic responses that are similar to those in Avena shoots. The pulvinus is a highly specialized organ with radial symmetry and is made up of epidermal, vascular, parenchymatous and collenchymatous tissues. Statoliths, which are confined to parenchyma cells around the vascular bundles, sediment towards the gravitational field within 10–15 min of geotropic stimulation. Collenchymatous cells occur as prominent bundle caps, and in Avena , they occupy about 30% of the volume of the pulvinus. Geotropic stimulation causes a 3- to 5-fold increase in the length of the cells on the side nearest to the center of the gravitational field. Growth can also be initiated in vertically-held pulvini by the application of indole-3-acetic acid, 1-naphthaleneacetic acid or 2.4-dichlorophenoxyacetic acid. 2.3.5.-triiodobenzoic acid interferes with growth response produced by geotropic stimulation as well as with the response caused by auxin application. Gibberellic acid and kinetin have no visible effect on the growth of the pulvinus. Polarization microscopy shows a unique, non-uniform stretching of the elongating collenchymatous cells. Nonelongated collenchymatous cells appear uniformally anisotropic. After geotropic stimulation or auxin application, they appear alternately anisotropic and almost isotropic. Such a pattern of cell elongation is also observed in collenchyma cells of geotropically-stimulated shoots of Rumex acetosa L., a dicotyledon.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47463/1/425_2004_Article_BF00385422.pd