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Kassu Desta,1,2 Eleni Aklillu,3 Yirgu Gebrehiwot,4 Fikre Enquselassie5 ,† Daire Cantillon,6 Leena Al-Hassan,6 James R Price,6 Melanie J Newport,6 Gail Davey,5,6 Yimtubezenash Woldeamanuel1 1Department of Microbiology, Immunology, and Parasitology, School of Medicine, College of Health Sciences (CHS), Addis Ababa University (AAU), Addis Ababa, Ethiopia; 2Department of Medical Laboratory Sciences, CHS, AAU, Addis Ababa, Ethiopia; 3Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute, Karolinska, Sweden; 4Department of Obstetrics and Gynecology, School of Medicine, CHS, AAU, Addis Ababa, Ethiopia; 5School of Public Health, CHS, AAU, Addis Ababa, Ethiopia; 6Department of Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK†Fikre Enquselassie passed away on October 27, 2019Correspondence: Kassu Desta, Tel +251 911107099, Email kassudesta2020@gmail.comBackground: Staphylococcus aureus is a major human pathogen and causes healthcare and community-acquired infection. Data on the extent of MRSA colonization among health-care workers (HCWs) in sub-Saharan Africa are limited. Hence, we determined the burden of MRSA colonisation among HCWs and administrative staff in Tikur Anbessa Specialised Hospital (TASH), College of Health Sciences (CHS), Addis Ababa University, Ethiopia.Methods: Using a cross-sectional study design, participants were screened for MRSA colonisation between June 2018 and August 2019 using nasal swabs. The swabs were analysed using standard laboratory methods including antibiotic resistance gene, mecA. Anonymised sociodemographic data were collected by pretested questionnaires to evaluate HCWs factors associated with MRSA carriage.Results: A total of 588 HCWs and 468 administrative staff were screened for MRSA. Women were over-represented. Overall, 49.1% (289/588) of HCWs were nurses and 25% (117/468) of the administrative staff were cleaners or laundry workers. Overall, 138 S. aureus isolates were retrieved from the nasal swabs of both groups (16.3%, 96/588 from HCWs). The burden of MRSA colonisation was 4.8% (28/580, 95% CI: 3.1– 6.5%) among HCWs compared to 0.2% (1/468, 95% CI: 0.18– 0.6%) of administrative staff (p value < 0.05). The majority of S. aureus and all MRSA isolates were resistant to penicillin. Isolates from HCWs were more resistant to tested antibiotics than administrative staff (P-value < 0.05).Conclusion: This is the first report in Ethiopia on MRSA colonization using mecA and revealed that; (i) overall carriage rates of MRSA in HCWs are comparable with observations reported in some other countries and (ii) HCWs exhibit a higher burden of MRSA carriage than administrative staff. Our data support strategic screening of MRSA and antimicrobial stewardship for better intervention measures.Keywords: MRSA, HCWs, administrative staff, mecA, TASH, Ethiopia

Bacille Calmette-Guérin (BCG) vaccination induces a marked increase in the interferon (IFN)-gamma response to Mycobacterium tuberculosis purified protein derivative (Mtb PPD) in UK adolescents, but not in Malawian adolescents. We hypothesized that Mtb PPD-induced IFN-gamma after BCG vaccination would be similar in infants from these 2 countries. Infants were vaccinated with BCG during the first 3-13 weeks of life. Three months after BCG vaccination, 51 (100%) of 51 UK infants had an IFN-gamma response to Mtb PPD, compared to 41 (53%) of 78 of Malawian infants, in whom responses varied according to their season of birth. We conclude that population differences in immune responses after BCG vaccination are observed among infants, as well as among young adults. [ABSTRACT FROM AUTHOR]

Background: Immune responses are complex traits influenced by genetic and environmental factors. We previously reported that genetic factors control early antibody responses to vaccines in Gambian infants. For the present study, we evaluated the determinants of the memory phase of immunoglobulin G (IgG) responses.Methods: Antibody responses to tetanus toxoid (TT), measles vaccines, and environmental antigens (total IgG levels) were measured in 210 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variations in response.Results: In contrast to antibody responses measured in infants at age 5 months, 1 month after immunization, no significant contribution of genetic factors to anti-TT antibody and total IgG levels was detected at age 12 months. Genetic factors controlled measles antibody responses in 12-month-old infants, which indicates that the increasing influence of environmental determinants on anti-TT responses was not related to the older age of the children but, rather, to the time elapsed since immunization. Environmental factors also predominantly controlled affinity maturation and the production of high-avidity antibodies to TT.Conclusions: Genetic determinants control the early phase of the vaccine antibody response in Gambian infants, whereas environmental determinants predominantly influence antibody persistence and avidity maturation. [ABSTRACT FROM AUTHOR]

Available evidences suggest that podoconiosis is triggered by long term exposure of bare feet to volcanic red clay soil particles. Previous genome-wide studies in Ethiopia showed association between the HLA class II region and disease susceptibility. However, functional relationships between the soil trigger, immunogenetic risk factors and the immunological basis of the disease are uncharted. Therefore, we aimed to characterise the immune profile and gene expression of podoconiosis patients relative to endemic healthy controls. Peripheral blood immunophenotyping of T cells indicated podoconiosis patients had significantly higher CD4 and CD8 T cell surface HLA-DR expression compared to healthy controls while CD62L expression was significantly lower. The levels of the activation markers CD40 and CD86 were significantly higher on monocytes and dendritic cell subsets in patients compared to the controls. RNA sequencing gene expression data indicated higher transcript levels for activation, scavenger receptors, and apoptosis markers while levels were lower for histones, T cell receptors, variable, and constant immunoglobulin chain in podoconiosis patients compared to healthy controls. Our finding provides evidence that podoconiosis is associated with high levels of immune activation and inflammation with over-expression of genes within the pro-inflammatory axis. This offers further support to a working hypothesis of podoconiosis as soil particle-driven, HLA-associated disease of immunopathogenic aetiology., (© 2024. The Author(s).)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Mycetoma is a chronic, progressively destructive disease of subcutaneous tissues and bones caused by certain species of bacteria or fungi. We conducted a cross-sectional community-based study alongside mapping of mycetoma in five administrative units with high mycetoma endemicity in the Eastern Sennar Locality, Sennar State, Sudan., Methods: A household survey was administered which included questions about the household members, household characteristics, economic activity and history of mycetoma. A clinical examination was conducted on all members of the household. If mycetoma was suspected, an individual questionnaire was completed collecting demographic, clinical and epidemiological data as well as information on the use of health care and associated costs. Geographical coordinates and photos of the lesions were taken, and the affected persons were referred to the medical centre for confirmation of the diagnosis and treatment. We compared the characteristics of households with confirmed cases of mycetoma with those without confirmed cases, and individuals with confirmed mycetoma with those in whom mycetoma was not confirmed., Results: In total 7,798 households in 60 villages were surveyed; 515 suspected cases were identified and 359 cases of mycetoma were confirmed. Approximately 15% of households with mycetoma had more than one household member affected by this disease. Households with mycetoma were worse off with respect to water supply, toilet facilities, electricity and electrical appliances compared to the survey households. Only 23% of study participants with mycetoma had sought professional help. Of these, 77% of patients travelled an average of six hours to visit a medical facility. More than half of patients had to pay towards their treatment. The estimated average cost of treatment was 26,957 Sudanese pounds per year (566 US dollars, exchange rate 2018)., Conclusions: Results of this survey suggest that agricultural practices and reduced access to sanitation and clean water can be risk factors in developing mycetoma. Poor access to health care and substantial financial costs were barriers to seeking treatment for mycetoma., Competing Interests: The authors have declared that no competing interests exist.

The declared aim of "personalized", "stratified" or "precision" approaches is to place individual variation, as ascertained through genomic and various other biomarkers, at the heart of Scientific Medicine using it to predict risk of disease or response to therapy and to tailor interventions and target therapies so as to maximize benefit and minimize risk for individual patients and efficiency for the health care system overall. It is often contrasted to current practices for which the scientific base is rooted in concepts of a "universal biology" and a "typical" or "average patient" and in which variation is ignored. Yet both approaches equally overlook the hierarchical nature of human variation and the critical importance of differences between populations. Impact of genetic heterogeneity has to be seen within that context to be meaningful and subsequently useful. In Africa such complexity is compounded by the high effective size of its populations, their diverse histories and the diversity of the environmental terrains they occupy, rendering analysis of gene environment interactions including the establishment of phenotype genotype correlations even more cumbersome. Henceforth "Individualized" methods and approaches can only magnify the shortcomings of universal approaches if adopted without due regard to these complexities. In the current perspective we review examples of potential hurdles that may confront biomedical scientists and analysts in genomic medicine in clinical and public health genomics in Africa citing specific examples from the current SARS-COV2 pandemic and the challenges of establishing reference biobanks and pharmacogenomics reference values., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hussein, Hamad, Newport and Ibrahim.)

Background: Mycetoma is a neglected tropical disease that is reported worldwide and Sudan has the highest reported number of mycetoma infections across the globe. The incidence, prevalence and burden of mycetoma globally are not precisely known and its risk factors remain largely unelucidated., Methods: This study aimed to identify the environmental predictors of fungal and bacterial mycetoma in Sudan and to identify areas of the country where these niche predictors are met. Demographic and clinical data from confirmed mycetoma patients seen at the Mycetoma Research Centre from 1991 to 2018 were included in this study. Regression and machine learning techniques were used to model the relationships between mycetoma occurrence in Sudan and environmental predictors., Results: The strongest predictors of mycetoma occurrence were aridity, proximity to water, low soil calcium and sodium concentrations and the distribution of various species of thorny trees. The models predicted the occurrence of eumycetoma and actinomycetoma in the central and southeastern states of Sudan and along the Nile river valley and its tributaries., Conclusion: Our results showed that the risk of mycetoma in Sudan varies geographically and is linked to identifiable environmental risk factors. Suitability maps are intended to guide health authorities, academic institutes and organisations involved in planning national scale surveys for early case detection and management, leading to better patient treatment, prevention and control of mycetoma., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Podoconiosis is a type of tropical lymphedema that is clinically distinguished from lymphatic filariasis (LF) because it is ascending and commonly bilateral but asymmetric. The disease is a result of a genetically determined inflammatory reaction to long-term exposure to mineral particles in irritant red clay soils derived mainly from volcanic soils. We conducted the first nationwide mapping of the prevalence and risk factors of podoconiosis in Kenya. We performed a population-based cross-sectional survey to determine the national prevalence of podoconiosis and included 6,228 individuals from 48 villages in 24 sub-counties across 15 counties. Participants answered a questionnaire about the history of symptoms compatible with podoconiosis, received a point-of-care antigen test, and underwent a physical examination if they had lymphedema. A confirmed case of podoconiosis was defined as a case in a resident of the study village who had lower limb bilateral and asymmetric lymphedema lasting more than 1 year, negative test results for Wuchereria bancrofti antigen, and other causes of lymphedema ruled out. Of all the individuals surveyed, 89 had lymphedema; of those, 16 of 6228 (0.3%; 95% confidence interval [CI], 0.1-0.5) were confirmed to have podoconiosis. A high prevalence of podoconiosis was found in western (Siaya, 3.1%; Busia, 0.9%) and central (Meru, 1.1%) regions, and a low prevalence was observed in northern (Marsabit, 0.2%), eastern (Makueni, 0.2%), and coastal (Tana River, 0.1%) regions. The identified risk factors were age 56 years or older (adjusted odds ratio [aOR], 5.66; 95% CI, 2.32-13.83; P < 0.001) and rarely wearing shoes (aOR, 18.92; 95% CI, 4.55-78.71; P < 0.001). These results indicated that the podoconiosis prevalence is low and localized in Kenya; therefore, elimination is achievable if appropriate disease prevention, management, and behavioral strategies are promoted.

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.

Mycobacteria naturally grow as corded biofilms in liquid media without detergent. Such detergent-free biofilm phenotypes may reflect the growth pattern of bacilli in tuberculous lung lesions. New strategies are required to treat tuberculosis, which is responsible for more deaths each year than any other bacterial disease. The lengthy 6-month regimen for drug-sensitive tuberculosis is necessary to remove antimicrobial drug tolerant populations of bacilli that persist through drug therapy. The role of biofilm-like growth in the generation of these sub-populations remains poorly understood despite the hypothesised clinical significance and mounting evidence of biofilms in pathogenesis. We adapt a three-dimensional Rotary Cell Culture System to model M. bovis BCG biofilm growth in low-shear detergent-free liquid suspension. Importantly, biofilms form without attachment to artificial surfaces and without severe nutrient starvation or environmental stress. Biofilm-derived planktonic bacilli are tolerant to isoniazid and streptomycin, but not rifampicin. This phenotypic drug tolerance is lost after passage in drug-free media. Transcriptional profiling reveals induction of cell surface regulators, sigE and BCG&#95;0559c alongside the ESX-5 secretion apparatus in these low-shear liquid-suspension biofilms. This study engineers and characterises mycobacteria grown as a suspended biofilm, illuminating new drug discovery pathways for this deadly disease.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4-123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes., Competing Interests: The authors have declared that no competing interests exist.

Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify 'at-risk' individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future., Competing Interests: The authors have declared that no competing interests exist.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The tenth conference of the African Society of Human Genetics was held in Egypt with the theme "Human Genetics and Genomics in Africa: Challenges for Both Rare and Common Genetic Disorders." Current research was presented, and we discussed visions for the future of genomic research on the African continent. In this report, we summarize the presented scientific research within and relevant to Africa as presented by both African and non-African scientists. We also discuss the current situation concerning genomic medicine and genomic research within the continent, difficulties in implementing genetic services and genomic medicine in Africa, and a road map to overcome those difficulties and meet the needs of the African researchers and patients.

Background: Podoconiosis is a type of elephantiasis characterised by swelling of the lower legs. It is often confused with other causes of tropical lymphedema and its global distribution is uncertain. Here we synthesise the available information on the presence of podoconiosis to produce evidence consensus maps of its global geographical distribution., Methods and Findings: We systematically searched available data on podoconiosis in SCOPUS and MEDLINE from inception, updated to 10 May, 2019, and identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used the number of cases reported in studies and prevalence data with geographical locations. We then developed an index to assess evidence quality and reliability, assigning each country an evidence consensus score. Using these summary scores, we then developed a contemporary global map of national-level podoconiosis status. There is evidence of podoconiosis in 17 countries (12 in Africa, three in Latin America, and two in Asia) and consensus on presence in six countries (all in Africa). We have identified countries where surveillance is required to further define the presence or absence of podoconiosis. We have highlighted areas where evidence is currently insufficient or conflicting, and from which more evidence is needed., Conclusion: The global distribution of podoconiosis is not clearly known; the disease extent and limits provided here inform the best contemporary map of the distribution of podoconiosis globally from available data. These results help identify surveillance needs, direct future mapping activities, and inform prevention plans and burden estimation of podoconiosis., Competing Interests: The authors have declared that no competing interests exist.

Background: Podoconiosis is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils. It results in leg swelling, commonly complicated by acute dermatolymphangioadenitis (ADLA), characterised by severe pain, fever and disability., Methods: We conducted cost-effectiveness and social outcome analyses of a pragmatic, randomised controlled trial of a hygiene and foot-care intervention for people with podoconiosis in the East Gojjam zone of northern Ethiopia. Participants were allocated to the immediate intervention group or the delayed intervention group (control). The 12-month intervention included training in foot hygiene, skin care, bandaging, exercises, and use of socks and shoes, and was supported by lay community assistants. The cost-effectiveness analysis was conducted using the cost of productivity loss due to acute dermatolymphangioadenitis. Household costs were not included. Health outcomes in the cost-effectiveness analysis were: the incidence of ADLA episodes, health-related quality of life captured using the Dermatology Life Quality Index (DLQI), and disability scores measured using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)., Results: The cost of the foot hygiene and lymphoedema management supplies was 529 ETB (69 I$, international dollars) per person per year. The cost of delivery of the intervention as part of the trial, including transportation, storage, training of lay community assistants and administering the intervention was 1,890 ETB (246 I$) per person. The intervention was effective in reducing the incidence of acute dermatolymphangioadenitis episodes and improving DLQI scores, while there were no significant improvements in the disability scores measured using WHODAS 2.0. In 75% of estimations, the intervention was less costly than the control. This was due to improved work productivity. Subgroup analyses based on income group showed that the intervention was cost-effective (both less costly and more effective) in reducing the number of acute dermatolymphangioadenitis episodes and improving health-related quality of life in families with monthly income <1,000 ETB (130 I$). For the subgroup with family income ≥1,000 ETB, the intervention was more effective but more costly than the control., Conclusions: Whilst there is evident benefit of the intervention for all, the economic impact would be greatest for the poorest., Competing Interests: The authors have declared that no competing interests exist.

Background: Podoconiosis is a type of tropical lymphoedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. Reliable and detailed data on the prevalence and distribution of podoconiosis are scarce. We aimed to fill this data gap by doing a nationwide community-based study to estimate the number of cases throughout Rwanda., Methods: We did a population-based cross-sectional survey to determine the national prevalence of podoconiosis. A podoconiosis case was defined as a person with bilateral, asymmetrical lymphoedema of the lower limb present for more than 1 year, who tested negative for Wuchereria bancrofti antigen (determined by Filariasis Test Strip) and specific IgG4 (determined by Wb123 test), and had a history of any of the associated clinical signs and symptoms. All adults (aged ≥15 years) who resided in any of the 30 districts of Rwanda for 10 or more years were invited at the household level to participate. Participants were interviewed and given a physical examination before Filariasis Test Strip and Wb123 testing. We fitted a binomial mixed model combining the site-level podoconiosis prevalence with continuous environmental covariates to estimate prevalence at unsampled locations. We report estimates of cases by district combining our mean predicted prevalence and a contemporary gridded map of estimated population density., Findings: Between June 12, and July 28, 2017, 1 360 612 individuals-719 730 (53%) women and 640 882 (47%) men-were screened from 80 clusters in 30 districts across Rwanda. 1143 individuals with lymphoedema were identified, of whom 914 (80%) had confirmed podoconiosis, based on the standardised diagnostic algorithm. The overall prevalence of podoconiosis was 68·5 per 100 000 people (95% CI 41·0-109·7). Podoconiosis was found to be widespread in Rwanda. District-level prevalence ranged from 28·3 per 100 000 people (16·8-45·5, Nyarugenge, Kigali province) to 119·2 per 100 000 people (59·9-216·2, Nyamasheke, West province). Prevalence was highest in districts in the North and West provinces: Nyamasheke, Rusizi, Musanze, Nyabihu, Nyaruguru, Burera, and Rubavu. We estimate that 6429 (95% CI 3938-10 088) people live with podoconiosis across Rwanda., Interpretation: Despite relatively low prevalence, podoconiosis is widely distributed geographically throughout Rwanda. Many patients are likely to be undiagnosed and morbidity management is scarce. Targeted interventions through a well coordinated health system response are needed to manage those affected. Our findings should inform national level planning, monitoring, and implementation of interventions., Funding: Wellcome Trust., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non-muscle-invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin responsiveness of CD4 + T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4 + T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin-induced secreted mediators were measured by electrochemiluminescence. We correlated the results with recurrence-free patient survival 6 months after induction. A tuberculin-induced, secreted, IL2 concentration > 250 pg/mL was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6% of cases. In 50% of patients later experiencing recurrence, but not in any of the recurrence-free survivors, IL2 secretion was < 120 pg/mL. Other parameters predicting recurrence-free survival included secreted IFNγ (AUC = 0.796, P = 0.002) and the frequencies of TNF-producing (TNF + ) CD4 + T cells (AUC = 0.745, P = 0.010). "Polyfunctional" CD4 + T cells (IFNγ + /IL2 + /TNF + ) were significantly associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the amount of IL2 secretion from CD4 + T cells after overnight in vitro incubation with tuberculin predicted the outcome of BCG immunotherapy. As many as half of potential BCG failures could be identified before induction therapy is begun, enabling better choices regarding treatment. Cancer Immunol Res; 6(10); 1212-9. ©2018 AACR ., (©2018 American Association for Cancer Research.)

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-to-house 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 socio-economic 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.

Background: Podoconiosis (also known as endemic, non-filarial elephantiasis) affects about 4 million subsistence farmers in tropical Africa. Poor awareness of the condition and inadequate evidence for the efficacy of treatment mean that no government in an endemic country yet offers lymphoedema management for patients with podoconiosis. Among patients with filarial lymphoedema, trials suggest that limb care is effective in reducing the most disabling sequelae: episodes of acute dermatolymphangioadenitis. We aimed to test the hypothesis that a simple, inexpensive lymphoedema management package would reduce the incidence of acute dermatolymphangioadenitis in adult patients with podoconiosis in northern Ethiopia., Methods: We did a pragmatic randomised controlled trial at health posts and health centres in 18 sub-districts of Aneded woreda (district) in Amhara, northern Ethiopia. Participants were adults aged 18 years and older, had a diagnosis of at least stage 2 podoconiosis (persistent lymphoedema) and a negative antigen test for filariasis, and intended to remain within Aneded woreda for the duration of the trial. Patients were randomly assigned (1:1) to either receive a package containing instructions for foot hygiene, skin care, bandaging, exercises, and use of socks and shoes, with support by lay Community Podoconiosis Agents at monthly meetings (intervention group) or to receive no intervention (control group). Participants were aware of their group assignment, but researchers doing all analyses were masked to treatment group. The primary outcome was incidence of acute dermatolymphangioadenitis episodes in the total period of observation of each participant, measured by use of validated patient self-reported pictorial diaries. This trial was registered with the International Standard Randomised Controlled Trials Number Register, number ISRCTN67805210., Findings: Between Dec 1, 2014, and June 30, 2015, 1339 patients were screened, and 696 patients were enrolled and randomly allocated to treatment groups. We allocated 350 patients to the intervention group and 346 patients to the control group. 321 (92%) patients from the intervention group and 329 (95%) patients from the control group provided follow-up results at 12 months. During the 12 months of follow-up, 16 550 new episodes of acute dermatolymphangioadenitis occurred during 765·2 person-years. The incidence of acute dermatolymphangioadenitis was 19·4 episodes per person-year (95% CI 18·9-19·9) in the intervention group and 23·9 episodes per person-year (23·4-24·4) in the control group. The ratio of incidence rate in the intervention group to that of the control group was 0·81 (0·74 to 0·89; p<0·0001), with a rate difference of -4·5 (-5·1 to -3·8) episodes per person-year. No serious adverse events related to the intervention were reported., Interpretation: A simple, inexpensive package of lymphoedema self-care is effective in reducing the frequency and duration of acute dermatolymphangioadenitis. We recommend its implementation by the governments of endemic countries., Funding: Joint Global Health Trials scheme (from the Wellcome Trust, the UK Medical Research Council, and UK Aid)., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Understanding the number of cases of podoconiosis, its geographical distribution and the population at risk are crucial to estimating the burden of this disease in endemic countries. We assessed each of these using nationwide data on podoconiosis prevalence in Cameroon., Methods: We analysed data arising from two cross-sectional surveys in Cameroon. The dataset was combined with a suite of environmental and climate data and analysed within a robust statistical framework, which included machine learning-based approaches and geostatistical modelling. The environmental limits, spatial variation of predicted prevalence, population at risk and number of cases of podoconiosis were each estimated., Results: A total of 214 729 records of individuals screened for podoconiosis were gathered from 748 communities in all 10 regions of Cameroon. Of these screened individuals, 882 (0.41%; 95% CI 0.38 to 0.44) were living with podoconiosis. High environmental suitability for podoconiosis was predicted in three regions of Cameroon (Adamawa, North West and North). The national population living in areas environmentally suitable for podoconiosis was estimated at 5.2 (95% CI 4.7 to 5.8) million, which corresponds to 22.3% of Cameroon's population in 2015. Countrywide, in 2015, the number of adults estimated to be suffering from podoconiosis was 41 556 (95% CI, 1170 to 240 993). Four regions (Central, Littoral, North and North West) contributed 61.2% of the cases., Conclusion: In Cameroon, podoconiosis is more widely distributed geographically than was initially expected. The number of cases and the population at risk are considerable. Expanding morbidity management and follow-up of cases is of utmost necessity. Promotion of footwear use and regular foot hygiene should be at the forefront of any intervention plan., Competing Interests: Competing interests: None declared.

Background: Podoconiosis is one of the few diseases that could potentially be eliminated within one generation. Nonetheless, the global distribution of the disease remains largely unknown. The global atlas of podoconiosis was conceived to define the epidemiology and distribution of podoconiosis through dedicated surveys and assembling the available epidemiological data., Methods: We have synthesized the published literature on the epidemiology of podoconiosis. Through systematic searches in SCOPUS and MEDLINE from inception to February 14, 2018, we identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used case reports and presence data. For a study to be included in the prevalence synthesis, it needed to be a population-based survey that involved all residents within a specific area. Studies that did not report original data were excluded. We undertook descriptive analyses of the extracted data. This study is registered with PROSPERO, number CRD42018084959., Results: We identified 3,260 records, of which 27 studies met the inclusion criteria. Podoconiosis was described to exist or be endemic in 32 countries, 18 from the African Region, 3 from Asia and 11 from Latin America. Overall, podoconiosis prevalence ranged from 0·10% to 8.08%, was highest in the African region, and was substantially higher in adults than in children and adolescents. The highest reported prevalence values were in Africa (8.08% in Cameroon, 7.45% in Ethiopia, 4.52% in Uganda, 3.87% in Kenya and 2.51% in Tanzania). In India, a single prevalence of 0.21% was recorded from Manipur, Mizoram and Rajasthan states. None of the Latin American countries reported prevalence data., Conclusion: Our data suggest that podoconiosis is more widespread in the African Region than in the rest of the regions, although this could be related to the fact that most podoconiosis epidemiological research has been focused in the African continent. The assembled dataset confirms that comprehensive podoconiosis control strategies such as promotion of footwear and personal hygiene are urgently needed in endemic parts of Africa. Mapping, active surveillance and a systematic approach to the monitoring of disease burden must accompany the implementation of podoconiosis control activities.

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.

Background: In 2011, the World Health Organization recognized podoconiosis as one of the neglected tropical diseases. Nonetheless, the number of people with podoconiosis and the geographical distribution of the disease is poorly understood. Based on a nationwide mapping survey and geostatistical modelling, we predict the prevalence of podoconiosis and estimate the number of cases across Ethiopia., Methods: We used nationwide data collected in Ethiopia between 2008 and 2013. Data were available for 141,238 individuals from 1,442 villages in 775 districts from all nine regional states and two city administrations. We developed a geostatistical model of podoconiosis prevalence among adults (individuals aged 15 years or above), by combining environmental factors. The number of people with podoconiosis was then estimated using a gridded map of adult population density for 2015., Results: Podoconiosis is endemic in 345 districts in Ethiopia: 144 in Oromia, 128 in Southern Nations, Nationalities and People's [SNNP], 64 in Amhara, 4 in Benishangul Gumuz, 4 in Tigray and 1 in Somali Regional State. Nationally, our estimates suggest that 1,537,963 adults (95% confidence intervals, 290,923-4,577,031 adults) were living with podoconiosis in 2015. Three regions (SNNP, Oromia and Amhara) contributed 99% of the cases. The highest proportion of individuals with podoconiosis resided in the SNNP (39%), while 32% and 29% of people with podoconiosis resided in Oromia and Amhara Regional States, respectively. Tigray and Benishangul Gumuz Regional States bore lower burdens, and in the remaining regions, podoconiosis was almost non-existent.  Discussion: The estimates of podoconiosis cases presented here based upon the combination of currently available epidemiological data and a robust modelling approach clearly show that podoconiosis is highly endemic in Ethiopia. Given the presence of low cost prevention, and morbidity management and disability prevention services, it is our collective responsibility to scale-up interventions rapidly., Competing Interests: Competing interests: No competing interests were disclosed.

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.

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., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences., Results: Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (p<2.2e-16) than HK gene promoters. The entropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes., Conclusion: Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The fixation index F(st) plays a central role in ecological and evolutionary genetic studies. The estimators of Wright ([Formula: see text]), Weir and Cockerham ([Formula: see text]), and Hudson et al. ([Formula: see text]) are widely used to measure genetic differences among different populations, but all have limitations. We propose a minimum variance estimator [Formula: see text] using [Formula: see text] and [Formula: see text]. We tested [Formula: see text] in simulations and applied it to 120 unrelated East African individuals from Ethiopia and 11 subpopulations in HapMap 3 with 464,642 SNPs. Our simulation study showed that [Formula: see text] has smaller bias than [Formula: see text] for small sample sizes and smaller bias than [Formula: see text] for large sample sizes. Also, [Formula: see text] has smaller variance than [Formula: see text] for small Fst values and smaller variance than [Formula: see text] for large F(st) values. We demonstrated that approximately 30 subpopulations and 30 individuals per subpopulation are required in order to accurately estimate F(st).

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.

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.