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      Global epidemiology of podoconiosis: A systematic review

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          Abstract

          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.

          Author summary

          Podoconiosis is one of the Neglected Tropical Diseases, and causes painful and massive swelling of the lower legs. Despite the importance of the disease, its global distribution and epidemiology are poorly understood. We conducted a systematic review to assess the global epidemiology of podoconiosis. We found that podoconiosis was described to exist or be endemic in 32 countries, 18 from Africa, 3 from Asia and 11 from Latin America. Almost all prevalence data recorded corresponded to the African region. None of the Latin American countries reported prevalence data, although some countries are suspected to be endemic. We recommend that comprehensive podoconiosis control strategies such as promotion of footwear and personal hygiene are urgently needed in endemic countries in the African Region. Mapping, active surveillance and a systematic approach to the monitoring of disease burden must accompany the implementation of podoconiosis control activities.

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          Most cited references59

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          HLA class II locus and susceptibility to podoconiosis.

          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%). 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. 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. 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.).
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            Podoconiosis: non-infectious geochemical elephantiasis.

            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.
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              Epidemiology and Individual, Household and Geographical Risk Factors of Podoconiosis in Ethiopia: Results from the First Nationwide Mapping

              Although podoconiosis is one of the major causes of tropical lymphoedema and is endemic in Ethiopia its epidemiology and risk factors are poorly understood. Individual-level data for 129,959 individuals from 1,315 communities in 659 woreda (districts) were collected for a nationwide integrated survey of lymphatic filariasis and podoconiosis. Blood samples were tested for circulating Wuchereria bancrofti antigen using immunochromatographic card tests. A clinical algorithm was used to reach a diagnosis of podoconiosis by excluding other potential causes of lymphoedema of the lower limb. Bayesian multilevel models were used to identify individual and environmental risk factors. Overall, 8,110 of 129,959 (6.2%, 95% confidence interval [CI] 6.1–6.4%) surveyed individuals were identified with lymphoedema of the lower limb, of whom 5,253 (4.0%, 95% CI 3.9–4.1%) were confirmed to be podoconiosis cases. In multivariable analysis, being female, older, unmarried, washing the feet less frequently than daily, and being semiskilled or unemployed were significantly associated with increased risk of podoconiosis. Attending formal education and living in a house with a covered floor were associated with decreased risk of podoconiosis. Podoconiosis exhibits marked geographical variation across Ethiopia, with variation in risk associated with variation in rainfall, enhanced vegetation index, and altitude.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                1 March 2018
                March 2018
                : 12
                : 3
                : e0006324
                Affiliations
                [1 ] Wellcome Trust Brighton and Sussex Centre for Global Health Research, Brighton and Sussex Medical School, Brighton, United Kingdom
                [2 ] School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia
                [3 ] Department of Disease Control, London School of Hygiene & Tropical Medicine, London, United Kingdom
                University of Tennessee, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-8526-6996
                http://orcid.org/0000-0001-9864-5058
                Article
                PNTD-D-18-00092
                10.1371/journal.pntd.0006324
                5849362
                29494642
                6576f73c-acdc-4c86-8277-587f4e04ba6b
                © 2018 Deribe et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 January 2018
                : 16 February 2018
                Page count
                Figures: 4, Tables: 2, Pages: 15
                Funding
                Funded by: Wellome Trust
                Award ID: 201900
                Award Recipient :
                KD is supported by a grant from the Wellcome Trust [grant number 201900] as part of his Intermediate Fellowship in Public Health and Tropical Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Parasitic Diseases
                Elephantiasis
                Podoconiosis
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Podoconiosis
                People and Places
                Geographical Locations
                Africa
                Ethiopia
                People and Places
                Geographical Locations
                Africa
                Cameroon
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Epidemiology
                Biology and Life Sciences
                Parasitology
                People and Places
                Geographical Locations
                Africa
                Uganda
                People and Places
                Geographical Locations
                Africa
                Custom metadata
                vor-update-to-uncorrected-proof
                2018-03-13
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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