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Background Understanding and accurately predicting the environmental limits, population at risk and burden of podoconiosis are critical for delivering targeted and equitable prevention and treatment services, planning control and elimination programs and implementing tailored case finding and surveillance activities. Methods This is secondary analysis of a nationwide podoconiosis mapping survey in Kenya. We combined national representative prevalence survey data of podoconiosis with climate and environmental data, overlayed with population figures in a geostatistical modelling framework, to predict the environmental suitability, population living in at-risk areas and number of cases of podoconiosis in Kenya. Results In 2020, the number of people living with podoconiosis in Kenya was estimated to be 9344 (95% uncertainty interval 4222 to 17 962). The distribution of podoconiosis varies by geography and three regions (Eastern, Nyanza and Western) represent >90% of the absolute number of cases. High environmental suitability for podoconiosis was predicted in four regions of Kenya (Coastal, Eastern, Nyanza and Western). In total, 2.2 million people live in at-risk areas and 4.2% of the total landmass of Kenya is environmentally predisposed for podoconiosis. Conclusions The burden of podoconiosis is relatively low in Kenya and is mostly restricted to certain small geographical areas. Our results will help guide targeted prevention and treatment approaches through local planning, spatial targeting and tailored surveillance activities. [ABSTRACT FROM AUTHOR]

Background Undertaking research and attaining informed consent can be challenging when there is political unrest and community mistrust. Rapid ethical appraisal (REA) is a tool that uses qualitative methods to explore sociocultural issues that may affect the ethical conduct of research. Methods We used REA in northeast Ethiopia shortly following a period of unrest, during which violence against researchers occurred, to assess stakeholder perceptions of research, researchers and the informed consent process. We held 32 in-depth interviews and 2 focus group discussions. Results Most community members had little awareness about podoconiosis or healthcare research. Convincing the community to donate blood for research is challenging due to association with HIV testing. The attack on researchers was mainly motivated by the community's mistrust of their intentions against the background of a volatile political situation. Social media contributed to the spread of misinformation. Lack of community engagement was also a key contributing factor. Conclusions Using REA, we identified potential barriers to the informed consent process, participant recruitment for data and specimen collection and the smooth conduct of research. Researchers should assess existing conditions in the study area and engage with the community to increase awareness prior to commencing their research activities. [ABSTRACT FROM AUTHOR]

Podoconiosis, a debilitating lymphoedema of the leg, results from barefoot exposure to volcanic clay soil in genetically susceptible individuals. A previous genome-wide association study (GWAS) conducted in the Wolaita ethnic group from Ethiopia showed association between single nucleotide polymorphisms (SNPs) in the HLA class II region and podoconiosis. We aimed to conduct a second GWAS in a new sample (N = 1892) collected from the Wolaita and two other Ethiopian populations, the Amhara and the Oromo, also affected by podoconiosis. Fourteen SNPs in the HLA class II region showed significant genome-wide association (P < 5.0 × 10−8) with podoconiosis. The lead SNP was rs9270911 (P = 5.51 × 10−10; OR 1.53; 95% CI 1.34–1.74), located near HLA-DRB1. Inclusion of data from the first GWAS (combined N = 2289) identified 47 SNPs in the class II HLA region that were significantly associated with podoconiosis (lead SNP also rs9270911 (P = 2.25 × 10−12). No new loci outside of the HLA class II region were identified in this more highly-powered second GWAS. Our findings confirm the HLA class II association with podoconiosis suggesting HLA-mediated abnormal induction and regulation of immune responses may have a direct role in its pathogenesis. [ABSTRACT FROM AUTHOR]

Background Podoconiosis is a tropical lymphoedema of the leg resulting from barefoot exposure to irritant volcanic soils. Approximately 4 million people are affected, mainly in African highland regions. The pathogenesis of this neglected tropical disease is still largely unknown, although HLA class II (HLAII) polymorphisms are associated with the disease. Methods NanoString technology was used to assess expression of 579 immune-related genes in formalin-fixed and paraffin-embedded lymph node archival samples from podoconiosis patients and unaffected controls. Results Forty-eight genes were upregulated and 21 downregulated in podoconiosis samples compared with controls. Gene ontology analysis showed differentially expressed genes to be closely related to major histocompatibility complex protein, cytokine and TNF receptor binding genes. Pathway enrichment analysis revealed involvement of lymphocyte activation, adaptive immunity, cytokine signalling, antigen processing and the IL-12 pathways. Conclusions This exploratory study reports a multiplex gene expression analysis in podoconiosis and shows upregulation of pro-inflammatory transcripts compatible with the notion of local, chronic immune activation in this HLAII-associated disease. Implicated pathways will inform future research into podoconiosis immunopathogenesis. [ABSTRACT FROM AUTHOR]

Podoconiosis is a non-infectious tropical lymphoedema causing swelling of the lower legs. Podoconiosis is associated with stigma, depression and reduced productivity, resulting in significant socio-economic impacts for affected individuals, families and communities. It is caused by barefoot exposure to soils and affects disadvantaged populations. Evidence from the past 5 y suggests that podoconiosis is amenable to public health interventions, e.g. footwear and hygiene-based morbidity management, which reduce acute clinical episodes. Although much has been learned in recent years, advances in care for these patients and worldwide control requires further reliable and relevant research. To develop a comprehensive global control strategy, the following key research priorities are important: better understanding of the global burden of podoconiosis through extended worldwide mapping, development of new point-of-care diagnostic methods and approaches to define the presence of the environmental characteristics that contribute to the development of the condition, improving treatment through an increased understanding of the pathogenesis of dermal changes over time, improved understanding of optimal ways of providing patient care at the national level, including research to optimize behavioural change strategies, determine the optimum package of care and integrate approaches to deliver robust surveillance, monitoring and evaluation of control programmes. [ABSTRACT FROM AUTHOR]

Background Difficulties in reliably diagnosing podoconiosis have severely limited the scale-up and uptake of the World Health Organization–recommended morbidity management and disability prevention interventions for affected people. We aimed to identify a set of clinical features that, combined into an algorithm, allow for diagnosis of podoconiosis. Methods We identified 372 people with lymphoedema and administered a structured questionnaire on signs and symptoms associated with podoconiosis and other potential causes of lymphoedema in northern Ethiopia. All individuals were tested for Wuchereria bancrofti –specific immunoglobulin G4 in the field using Wb123. Results Based on expert diagnosis, 344 (92.5%) of the 372 participants had podoconiosis. The rest had lymphoedema due to other aetiologies. The best-performing set of symptoms and signs was the presence of moss on the lower legs and a family history of leg swelling, plus the absence of current or previous leprosy, plus the absence of swelling in the groin, plus the absence of chronic illness (such as diabetes mellitus or heart or kidney diseases). The overall sensitivity of the algorithm was 91% (95% confidence interval [CI] 87.6 to 94.4) and specificity was 95% (95% CI 85.45 to 100). Conclusions We developed a clinical algorithm of clinical history and physical examination that could be used in areas suspected or endemic for podoconiosis. Use of this algorithm should enable earlier identification of podoconiosis cases and scale-up of interventions. [ABSTRACT FROM AUTHOR]

Background Podoconiosis is a non-infectious geochemical lymphoedema of the lower legs associated with a significant burden of morbidity. There are historical reports of podoconiosis in India, but its current endemicity status is uncertain. In this investigation we aimed to prioritise the selection of districts for pilot mapping of podoconiosis in India. Methods Through a consultative workshop bringing together expert opinion on podoconiosis with public health and NTDs in India, we developed a framework for the prioritisation of pilot areas. The four criteria for prioritisation were predicted environmental suitability for podoconiosis, higher relative poverty, occurrence of lymphoedema cases detected by the state health authorities and absence of morbidity management and disability prevention (MMDP) services provided by the National Programme for Elimination of Lymphatic Filariasis. Results Environmental suitability for podoconiosis in India was predicted to be widespread, particularly in the mountainous east and hilly southwest of the country. Most of the districts with higher levels of poverty were in the central east and central west. Of 286 districts delineated by state representatives, lymphoedema was known to the health system in 189 districts and not recorded in 80. Information on MMDP services was unavailable for many districts, but 169 were known not to provide such services. We identified 35 districts across the country as high priority for mapping based on these criteria. Conclusions Our results indicate widespread presence of conditions associated with podoconiosis in India, including areas with known lymphoedema cases and without MMDP services. This work is intended to support a rational approach to surveying for an unrecognised, geographically focal, chronic disease in India, with a view to scaling up to inform a national strategy if required. [ABSTRACT FROM AUTHOR]

Background Podoconiosis is one of the leading causes of lymphoedema-related morbidity in low-income settings, but little is known about the scale of its health and economic impact. This information is required to inform control programme planning and policy. In this study, we estimated the health and economic burden of podoconiosis in Ethiopia. Methods We developed a model to estimate the health burden attributed to podoconiosis in terms of the number of disability-adjusted life years (DALYs) and the economic burden. We estimated the economic burden by quantifying the treatment and morbidity-management costs incurred by the healthcare system in managing clinical cases, patients' out-of-pocket costs and their productivity costs. Results In 2017, there were 1.5 million cases of podoconiosis in Ethiopia, which corresponds to 172 073 DALYs or 182 per 100 000 people. The total economic burden of podoconiosis in Ethiopia is estimated to be US$213.2 million annually and 91.1% of this resulted from productivity costs. The average economic burden per podoconiosis case was US$136.9. Conclusions The national cost of podoconiosis is formidable. If control measures are scaled up and the morbidity burden reduced, this will lead to Ethiopia saving millions of dollars. Our estimates provide important benchmark economic costs to programme planners, policymakers and donors for resource allocation and priority setting. [ABSTRACT FROM AUTHOR]

Background While morbidity attributable to podoconiosis is relatively well studied, its pattern of mortality has not been established. Methods We compared the age-standardised mortality ratios (SMRs) of two datasets from northern Ethiopia: podoconiosis patients enrolled in a 1-y trial and a Health and Demographic Surveillance System cohort. Results The annual crude mortality rate per 1000 population for podoconiosis patients was 28.7 (95% confidence interval [CI] 17.3 to 44.8; n=663) while that of the general population was 2.8 (95% CI 2.3 to 3.4; n=44 095). The overall SMR for the study period was 6.0 (95% CI 3.6 to 9.4). Conclusions Podoconiosis patients experience elevated mortality compared with the general population and further research is required to understand the reasons. [ABSTRACT FROM AUTHOR]

Background: Although podoconiosis is endemic in Cameroon, little is known about its epidemiology and spatial distribution. Methods: This cross-sectional, population-based study enrolled all adults (=15 y) residing in the districts of the northwest region of Cameroon for 10 or more years. Participants were interviewed and had a physical examination. The study outcomes were prevalence estimates of lymphoedema and podoconiosis. House-tohouse screening was conducted by Community Health Implementers (CHIs). CHIs registered all individuals with lymphoedema and collected additional individual and household-related information. A panel of experts re-examined and validated all lymphoedema cases registered by CHIs. Results: Of the 439 781 individuals registered, 214 195 were adults (=15 y old) and had lived in the districts of the region for more than 10 y. A total of 2143 lymphoedema cases were identified by CHIs, giving a prevalence of lymphoedema of 1.0% (2143/214 195; 95% CI, 0.96-1.04). After review by experts, podoconiosis prevalence in the study area was 0.48% (1049/214 195; 95% CI, 0.46-0.52). The prevalence of podoconiosis varied by health district, from 0.16% in Oku to 1.92% in Bafut (p<0.05). A total of 374 patients were recruited by stratified random sampling from the validated CHIs' register to assess the clinical features and socioeconomic aspects of the disease. Patients reportedly were said to have first noticed swelling at an average age of 41.9±19.1 (range: 6-90 y). Most patients (86.1%; 315/366) complained of their legs suddenly becoming hot, red and painful. The majority (96.5%; 361/374) of the interviewees said they had worn shoes occasionally at some point in their life. The reported mean age at first shoe wearing was 14.2±10.1 (±SD, range 1-77 y). A high proportion (82.8%; 309/374) of the participants wore shoes at the time of interview. Of those wearing shoes, only 21.7% (67/309) were wearing protective shoes. Conclusion: This study provides an insight into the geographical distribution and epidemiology of podoconiosis in the North West region of Cameroon, yet management is limited. Evidence-informed targeted interventions are needed to manage people with lymphoedema. [ABSTRACT FROM AUTHOR]

Background: Podoconiosis is a non-filarial elephantiasis, which causes massive swelling of the lower legs. It was identified as a neglected tropical disease by WHO in 2011. Understanding of the geographical distribution of the disease is incomplete. As part of a global mapping of podoconiosis, this study was conducted in Cameroon to map the distribution of the disease. This mapping work will help to generate data on the geographical distribution of podoconiosis in Cameroon and contribute to the global atlas of podoconiosis. Methods: We used a multi‐stage sampling design with stratification of the country by environmental risk of podoconiosis. We sampled 76 villages from 40 health districts from the ten Regions of Cameroon. All individuals of 15-years old or older in the village were surveyed house-to-house and screened for lymphedema. A clinical algorithm was used to reliably diagnose podoconiosis, excluding filarial-associated lymphedema. Individuals with lymphoedema were tested for circulating Wuchereria bancrofti antigen and specific IgG4 using the Alere Filariasis Test Strips (FTS) test and the Standard Diagnostics (SD) BIOLINE lymphatic filariasis IgG4 test (Wb123) respectively, in addition to thick blood films. Presence of DNA specific to W. bancrofti was checked on night blood using a qPCR technique. Principal findings: Overall, 10,178 individuals from 4,603 households participated in the study. In total, 83 individuals with lymphedema were identified. Of the 83 individuals with lymphedema, two were found to be FTS positive and all were negative using the Wb123 test. No microfilaria of W. bancrofti were found in the night blood of any individual with clinical lymphedema. None were found to be positive for W. bancrofti using qPCR. Of the two FTS positive cases, one was positive for Mansonella perstans DNA, while the other harbored Loa loa microfilaria. Overall, 52 people with podoconiosis were identified after applying the clinical algorithm. The overall prevalence of podoconiosis was found to be 0.5% (95% [confidence interval] CI; 0.4–0.7). At least one case of podoconiosis was found in every region of Cameroon except the two surveyed villages in Adamawa. Of the 40 health districts surveyed, 17 districts had no cases of podoconiosis; in 15 districts, mean prevalence was between 0.2% and 1.0%; and in the remaining eight, mean prevalence was between 1.2% and 2.7%. Conclusions: Our investigation has demonstrated low prevalence but almost nationwide distribution of podoconiosis in Cameroon. Designing a podoconiosis control program is a vital next step. A health system response to the burden of podoconiosis is important, through case surveillance and morbidity management services. [ABSTRACT FROM AUTHOR]

Background: The suitability of using clinical assessment to identify patients with podoconiosis in endemic communities has previously been demonstrated. In this study, we explored the feasibility and accuracy of using Community Health Implementers (CHIs) for the large scale clinical screening of the population for podoconiosis in North-west Cameroon.Methods: Before a regional podoconiosis mapping, 193 CHIs and 50 health personnel selected from 6 health districts were trained in the clinical diagnosis of the disease. After training, CHIs undertook community screening for podoconiosis patients under health personnel supervision. Identified cases were later re-examined by a research team with experience in the clinical identification of podoconiosis.Results: Cases were identified by CHIs with an overall positive predictive value (PPV) of 48.5% [34.1-70%]. They were more accurate in detecting advanced stages of the disease compared to early stages; OR 2.07, 95% CI = 1.15-3.73, p = 0.015 for all advanced stages). Accuracy of detecting cases showed statistically significant differences among health districts (χ2 = 25.30, p = 0.0001).Conclusion: Podoconiosis being a stigmatized disease, the use of CHIs who are familiar to the community appears appropriate for identifying cases through clinical diagnosis. However, to improve their effectiveness and accuracy, more training, supervision and support are required. More emphasis must be given in identifying early clinical stages and in health districts with relatively lower PPVs. [ABSTRACT FROM AUTHOR]

Background: There is limited assessment of whether research participants in low-income settings are afforded a full understanding of the meaning of medical research. There may also be particular issues with the understanding of genetic research. We used a rapid ethical assessment methodology to explore perceptions surrounding the meaning of research, genetics and genetic research in north west Cameroon. Methods: Eleven focus group discussions (including 107 adults) and 72 in-depth interviews were conducted with various stakeholders in two health districts in north west Cameroon between February and April 2012. Results: Most participants appreciated the role of research in generating knowledge and identified a difference between research and healthcare but gave varied explanations as to this difference. Most participants' understanding of genetics was limited to concepts of hereditary, with potential benefits limited to the level of the individual or family. Explanations based on supernatural beliefs were identified as a special issue but participants tended not to identify any other special risks with genetic research. Conclusion: We demonstrated a variable level of understanding of research, genetics and genetic research, with implications for those carrying out genetic research in this and other low resource settings. Our study highlights the utility of rapid ethical assessment prior to complex or sensitive research. [ABSTRACT FROM AUTHOR]

The recent feasibility of genome-wide studies of adaptation in human populations has provided novel insights into biological pathways that have been affected by adaptive pressures. However, only a few African populations have been investigated using these genome-wide approaches. Here, we performed a genome-wide analysis for evidence of recent positive selection in a sample of 120 individuals of Wolaita ethnicity belonging to Omotic-speaking people who have inhabited the mid- and high-land areas of southern Ethiopia for millennia. Using the 11 HapMap populations as the comparison group, we found Wolaita-specific signals of recent positive selection in several human leukocyte antigen (HLA) loci. Notably, the selected loci overlapped with HLA regions that we previously reported to be associated with podoconiosis-a geochemical lymphedema of the lower legs common in the Wolaita area. We found selection signals in PPARA, a gene involved in energy metabolism during prolonged food deficiency. This finding is consistent with the dietary use of enset, a crop with high-carbohydrate and low-fat and -protein contents domesticated in Ethiopia subsequent to food deprivation 10 000 years ago, and with metabolic adaptation to high-altitude hypoxia. We observed novel selection signals in CDKAL1 and NEGR1, well-known diabetes and obesity susceptibility genes. Finally, the SLC24A5 gene locus known to be associated with skin pigmentation was in the top selection signals in the Wolaita, and the alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) associated with light skin pigmentation in Eurasian populations were of high frequency (47.9%) in this Omotic-speaking indigenous Ethiopian population. [ABSTRACT FROM AUTHOR]

Background: Ethiopia is assumed to have the highest burden of podoconiosis globally, but the geographical distribution and environmental limits and correlates are yet to be fully investigated. In this paper we use data from a nationwide survey to address these issues. Methodology: Our analyses are based on data arising from the integrated mapping of podoconiosis and lymphatic filariasis (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in western Ethiopia in 2008–2010. The integrated mapping used woreda (district) health offices’ reports of podoconiosis and LF to guide selection of survey sites. A suite of environmental and climatic data and boosted regression tree (BRT) modelling was used to investigate environmental limits and predict the probability of podoconiosis occurrence. Principal Findings: Data were available for 141,238 individuals from 1,442 communities in 775 districts from all nine regional states and two city administrations of Ethiopia. In 41.9% of surveyed districts no cases of podoconiosis were identified, with all districts in Affar, Dire Dawa, Somali and Gambella regional states lacking the disease. The disease was most common, with lymphoedema positivity rate exceeding 5%, in the central highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and Peoples regional states. BRT modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with population density and clay content. Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval [CI]: 20.2–51.7) million people (i.e. 43.8%; 95% CI: 25.3–64.8% of Ethiopia’s national population) lived in areas environmentally suitable for the occurrence of podoconiosis. Conclusions: Podoconiosis is more widespread in Ethiopia than previously estimated, but occurs in distinct geographical regions that are tied to identifiable environmental factors. The resultant maps can be used to guide programme planning and implementation and estimate disease burden in Ethiopia. This work provides a framework with which the geographical limits of podoconiosis could be delineated at a continental scale. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO), international donors and partners have emphasized the importance of integrated control of neglected tropical diseases (NTDs). Integrated mapping of NTDs is a first step for integrated planning of programmes, proper resource allocation and monitoring progress of control. Integrated mapping has several advantages over disease specific mapping by reducing costs and enabling co-endemic areas to be more precisely identified. We designed and conducted integrated mapping of lymphatic filariasis (LF) and podoconiosis in Ethiopia; here we present the methods, challenges and lessons learnt. Methods: Integrated mapping of 1315 communities across Ethiopia was accomplished within three months. Within these communities, 129,959 individuals provided blood samples that were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests (ICT). Wb123 antibody tests were used to further establish exposure to LF in areas where at least one ICT positive individual was detected. A clinical algorithm was used to reliably diagnose podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Results: A total of 8110 individuals with leg swelling were interviewed and underwent physical examination. Smartphones linked to a central database were used to collect data, which facilitated real-time data entry and reduced costs compared to traditional paper-based data collection approach; their inbuilt Geographic Positioning System (GPS) function enabled simultaneous capture of geographical coordinates. The integrated approach led to efficient use of resources and rapid mapping of an enormous geographical area and was well received by survey staff and collaborators. Mobile based technology can be used for such large scale studies in resource constrained settings such as Ethiopia, with minimal challenges. Conclusions: This was the first integrated mapping of podoconiosis and LF globally. Integrated mapping of podoconiosis and LF is feasible and, if properly planned, can be quickly achieved at nationwide scale. [ABSTRACT FROM AUTHOR]

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 the goal of 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 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 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) had positive associations with podoconiosis prevalence. Conclusions The quantities of smectite, mica and quartz within the soil was 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. [ABSTRACT FROM AUTHOR]

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 <1%), ‘medium’ (1–5%) and ‘high’ (>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. [ABSTRACT FROM AUTHOR]

Currently there is increasing recognition of the need for research in developing countries where disease burden is high. Understanding the role of local factors is important for undertaking ethical research in developing countries. We explored factors relating to information and communication during the process of informed consent, and the approach that should be followed for gaining consent. The study was conducted prior to a family-based genetic study among people with podoconiosis (non-filarial elephantiasis) in southern Ethiopia. Methodology/Principal Findings: We adapted a method of rapid assessment validated in The Gambia. The methodology was entirely qualitative, involving focus-group discussions and in-depth interviews. Discussions were conducted with podoconiosis patients and non-patients in the community, fieldworkers, researchers, staff of the local non-governmental organisation (NGO) working on prevention and treatment of podoconiosis, and community leaders. We found that the extent of use of everyday language, the degree to which expectations of potential participants were addressed, and the techniques of presentation of information had considerable impact on comprehension of information provided about research. Approaching podoconiosis patients via locally trusted individuals and preceding individual consent with community sensitization were considered the optimal means of communication. Prevailing poverty among podoconiosis patients, the absence of alternative treatment facilities, and participants' trust in the local NGO were identified as potential barriers for obtaining genuine informed consent. Conclusions: Researchers should evaluate the effectiveness of consent processes in providing appropriate information in a comprehensible manner and in supporting voluntary decision-making on a study-by-study basis. [ABSTRACT FROM AUTHOR]

Summary: This paper presents the proceedings of a scientific meeting that was held between the Royal Society of Tropical Medicine and Hygiene and the Norwegian Infectious Diseases Society at Ullevål University Hospital, Oslo on 20 June 2008. Seven speakers updated the audience on recent advances in relevant issues, including international maternal and child health, podoconiosis, schistosomiasis and HIV, leprosy in the UK, rapid diagnostic tests for malaria, delayed diagnosis of tuberculosis and the Global Filariasis Programme. The meeting ended with a series of case presentations. [Copyright &y& Elsevier]

Summary: This article reviews peer-reviewed publications and book chapters on the history, epidemiology, genetics, ecology, pathogenesis, pathology and management of podoconiosis (endemic non-filarial elephantiasis). Podoconiosis is a non-infectious geochemical elephantiasis caused by exposure of bare feet to irritant alkalic clay soils. It is found in at least 10 countries in tropical Africa, Central America and northwest India, where such soils coexist with high altitude, high seasonal rainfall and low income. Podoconiosis develops in men and women working barefoot on irritant soils, with signs becoming apparent in most patients by the third decade of life. Colloid-sized silicate particles appear to enter through the skin, are taken up into macrophages in the lower limb lymphatics and cause endolymphangitis and obliteration of the lymphatic lumen. Genetic studies provide evidence for high heritability of susceptibility to podoconiosis. The economic burden is significant in affected areas dependent on subsistence farming. Podoconiosis is unique in being an entirely preventable non-communicable disease. Primary prevention entails promoting use of footwear in areas of irritant soil; early stages are reversible given good foot hygiene, but late stages result in considerable economic and social difficulties, and require extended periods of elevation and occasionally nodulectomy. [Copyright &y& Elsevier]

Background: Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%). Methods: We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls. Results: We found a genomewide significant association of podoconiosis with the single-nucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P=1.42×10−9; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P=3.44×10−8), and suggestive associations (P<1.0×10−5) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701–DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis. Conclusions: Association between variants in HLA class II loci with podoconiosis (a noncommunicable disease) suggests that the condition may be a T-cell–mediated inflammatory disease and is a model for gene–environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.) [ABSTRACT FROM PUBLISHER]