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1.  Novel genomic signals of recent selection in an Ethiopian population 
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 that have inhabited the mid- and high-land areas of southern Ethiopia for millennia. Using the eleven HapMap populations as the comparison group, we found Wolaita-specific signals of recent positive selection in several 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 SNPs 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.
doi:10.1038/ejhg.2014.233
PMCID: PMC4351897  PMID: 25370040
natural selection; population genetics; human leukocyte antigen (HLA); metabolism; podoconiosis; Ethiopia
2.  Shrinking the Lymphatic Filariasis Map of Ethiopia: Reassessing the Population at Risk through Nationwide Mapping 
PLoS Neglected Tropical Diseases  2015;9(11):e0004172.
Background
Mapping of lymphatic filariasis (LF) is essential for the delineation of endemic implementation units and determining the population at risk that will be targeted for mass drug administration (MDA). Prior to the current study, only 116 of the 832 woredas (districts) in Ethiopia had been mapped for LF. The aim of this study was to perform a nationwide mapping exercise to determine the number of people that should be targeted for MDA in 2016 when national coverage was anticipated.
Methodology/Principal Finding
A two-stage cluster purposive sampling was used to conduct a community-based cross-sectional survey for an integrated mapping of LF and podoconiosis, in seven regional states and two city administrations. Two communities in each woreda were purposely selected using the World Health Organization (WHO) mapping strategy for LF based on sampling 100 individuals per community and two purposely selected communities per woreda. Overall, 130 166 people were examined in 1315 communities in 658 woredas. In total, 140 people were found to be positive for circulating LF antigen by immunochromatographic card test (ICT) in 89 communities. Based on WHO guidelines, 75 of the 658 woredas surveyed in the nine regions were found to be endemic for LF with a 2016 projected population of 9 267 410 residing in areas of active disease transmission. Combining these results with other data it is estimated that 11 580 010 people in 112 woredas will be exposed to infection in 2016.
Conclusions
We have conducted nationwide mapping of LF in Ethiopia and demonstrated that the number of people living in LF endemic areas is 60% lower than current estimates. We also showed that integrated mapping of multiple NTDs is feasible and cost effective and if properly planned, can be quickly achieved at national scale.
Author Summary
About 1.4 billion people are believed to be living in areas where Lymphatic filariasis (LF) is actively transmitted. However, the distribution of this disfiguring mosquito-borne parasitic disease and the true population at risk that can be targeted for treatment have not been defined for all endemic countries. By 2013, Ethiopia had not delineated the majority of the endemic implementation units that can be targeted for MDA. Here, we present the results of a nationwide mapping exercise conducted in 2013 to determine the number of people that should be targeted for treatment in 2016 when nationwide treatment coverage is expected. We adopted a two-stage cluster purposive sampling method for the integrated mapping of LF and podoconiosis in seven regional states and two city administrations. Using a WHO mapping strategy for LF, based on sampling 100 individuals per community ICT positive individuals (ICT+) and two purposely selected communities per district, we examined 130 166 people in 1315 communities in 658 districts. Only 140 people were found to be positive for LF antigen in 89 different communities. According to WHO guidelines, 75 of the 658 districts surveyed in the 9 regions were found to be LF endemic. Including the 37 endemic Woredas identified enprior to this study, 112 woredas across the country are known to be endemic for the disease with 11 580 010 people exposed to infection. However 6 190 482 of those resided in woredas where our survey results were borderline with only one ICT positive individual identified. We have demonstrated that the number of people living in areas of active LF transmission is at least 60% lower than current WHO estimates of 30 million. We also showed that integrated mapping of multiple NTDs is feasible and cost effective. However, the sensitivity of the diagnostic test used for LF is less than 100% and the identification of a single ICT positive adult may not provide evidence of disease transmission. Based on these limitations, and in addition to the restricted geographical representation of just two sites within a woreda, we recommend conducting research in the 45 woredas with borderline results (one ICT+) to shrink the denominator even further.
doi:10.1371/journal.pntd.0004172
PMCID: PMC4634982  PMID: 26539700
3.  The feasibility of eliminating podoconiosis 
Abstract
Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease.
doi:10.2471/BLT.14.150276
PMCID: PMC4645432  PMID: 26600613
4.  Measuring elimination of podoconiosis, endemicity classifications, case definition and targets: an international Delphi exercise 
International health  2015;7(5):306-316.
Background
Podoconiosis is one of the major causes of lymphoedema in the tropics. Nonetheless, currently there are no endemicity classifications or elimination targets to monitor the effects of interventions. This study aimed at establishing case definitions and indicators that can be used to assess endemicity, elimination and clinical outcomes of podoconiosis.
Methods
This paper describes the result of a Delphi technique used among 28 experts. A questionnaire outlining possible case definitions, endemicity classifications, elimination targets and clinical outcomes was developed. The questionnaire was distributed to experts working on podoconiosis and other neglected tropical diseases in two rounds. The experts rated the importance of case definitions, endemic classifications, elimination targets and the clinical outcome measures. Median and mode were used to describe the central tendency of expert responses. The coefficient of variation was used to describe the dispersals of expert responses.
Results
Consensus on definitions and indicators for assessing endemicity, elimination and clinical outcomes of podoconiosis directed at policy makers and health workers was achieved following the two rounds of Delphi approach among the experts.
Conclusions
Based on the two Delphi rounds we discuss potential indicators and endemicity classification of this disabling disease, and the ongoing challenges to its elimination in countries with the highest prevalence. Consensus will help to increase effectiveness of podoconiosis elimination efforts and ensure comparability of outcome data.
doi:10.1093/inthealth/ihv043
PMCID: PMC4550552  PMID: 26185194
Delphi; Elephantiasis; Elimination; Endemicity; Non-filarial elephantiasis; Podoconiosis
5.  Clinical and Pharmacogenomic Implications of Genetic Variation in a Southern Ethiopian Population 
The pharmacogenomics journal  2014;15(1):101-108.
Africa is home to genetically diverse human populations. We compared the genetic structure of the Wolaita ethnic population from southern Ethiopia (WETH, n=120) with HapMap populations using genome-wide variants. We investigated allele frequencies of 443 clinically and pharmacogenomically relevant genetic variants in WETH compared to HapMap populations. We found that WETH were genetically most similar to the Kenya Maasai and least similar to the Japanese in HapMap. Variant alleles associated with increased risk of adverse reactions to drugs used for treating tuberculosis (rs1799929 and rs1495741 in NAT2), thromboembolism (rs7294, rs9923231 and rs9934438 in VKORC1), and HIV/AIDS and solid tumors (rs2242046 in SLC28A1) had significantly higher frequencies in WETH compared to African ancestry HapMap populations. Our results illustrate that clinically relevant pharmacogenomic loci display allele frequency differences among African populations. We conclude that drug dosage guidelines for important global health diseases should be validated in genetically diverse African populations.
doi:10.1038/tpj.2014.39
PMCID: PMC4277706  PMID: 25069476
pharmacogenomics; global health; tuberculosis; HIV/AIDS; warfarin; Ethiopia
6.  Mapping and Modelling the Geographical Distribution and Environmental Limits of Podoconiosis in Ethiopia 
PLoS Neglected Tropical Diseases  2015;9(7):e0003946.
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.
Author Summary
Podoconiosis is a neglected tropical disease that results in swelling of the lower legs and feet. It is common among barefoot individuals with prolonged contact with irritant soils of volcanic origin. The disease causes significant social and economic burden. The disease can be prevented by consistent shoe wearing and regular foot hygiene. A pre-requisite for implementation of prevention and morbidity management is information on where the disease is endemic and the identification of priority areas. We undertook nationwide mapping of podoconiosis in Ethiopia covering 1442 communities in 775 districts all over Ethiopia. During the survey, individuals underwent a rapid-format antigen test for diagnosis of lymphatic filariasis and clinical history and physical examination for podoconiosis. A suite of environmental and climatic data and a method called boosted regression tree modelling was used to predict the occurrence of podoconiosis. Our survey results indicated that podoconiosis is more widespread in Ethiopia than previously estimated. The modelling indicated that the probability of podoconiosis occurrence increased with increasing altitude, precipitation and silt fraction of soil and decreased with more clay content and population density. The map showed that in 2010, 34.9 million people lived in areas environmentally suitable for the occurrence of podoconiosis in Ethiopia.
doi:10.1371/journal.pntd.0003946
PMCID: PMC4519246  PMID: 26222887
7.  Podoconiosis treatment in northern Ethiopia (GoLBet): study protocol for a randomised controlled trial 
Trials  2015;16:307.
Background
Podoconiosis is one of the forgotten types of leg swelling (elephantiasis) in the tropics. Unlike the other, better-known types of leg swelling, podoconiosis is not caused by any parasite, virus or bacterium, but by an abnormal reaction to minerals found in the clay soils of some tropical highland areas. Non-governmental Organizations (NGOs) have been responsible for the development of simple treatment methods without systematic evaluation of its effectiveness. It is essential that a large scale, fully controlled, pragmatic trial of the intervention is conducted. We aim to test the hypothesis that community-based treatment of podoconiosis lymphoedema reduces the frequency of acute dermatolymphangioadenitis episodes (‘acute attacks’) and improves other clinical, social and economic outcomes.
Methods/Design
This is a pragmatic, individually randomised controlled trial. We plan to randomly allocate 680 podoconiosis patients from the East Gojjam Zone in northern Ethiopia to one of two groups: ‘Standard Treatment’ or ‘Delayed Treatment’. Those randomised to standard treatment will receive the hygiene and foot-care intervention from May 2015 for one year, whereas those in the control arm will be followed through 2015 and be offered the intervention in 2016. The trial will be preceded by an economic context survey and a Rapid Ethical Assessment to identify optimal methods of conveying information about the trial and the approaches to obtaining informed consent preferred by the community. The primary outcome will be measured by recording patient recall and using a simple, patient-held diary that will be developed to record episodes of acute attacks. Adherence to treatment, clinical stage of disease, quality of life, disability and stigma will be considered secondary outcome measures. Other outcomes will include adverse events and economic productivity. Assessments will be made at baseline and at 3, 6, 9 and 12 months thereafter.
Discussion
The evidence is highly likely to inform implementation of the new master plan for integrated control of Neglected Tropical Diseases (NTDs), in which podoconiosis is identified as one of eight NTDs prioritised for control. Potentially, an estimated 3 million patients in Ethiopia will therefore benefit from the results of this trial.
Trial registration
International Standard Randomised Controlled Trial Number. Registration number: ISRCTN67805210. Date of registration: 24 January 2013.
doi:10.1186/s13063-015-0818-7
PMCID: PMC4504163  PMID: 26177812
Podoconiosis; Nonfilarial elephantiasis; Acute dermatolymphangioadenitis; Randomised controlled trial; Neglected tropical disease; Stigma; Disability
8.  Measuring elimination of podoconiosis, endemicity classifications, case definition and targets: an international Delphi exercise 
International Health  2015;7(5):306-316.
Background
Podoconiosis is one of the major causes of lymphoedema in the tropics. Nonetheless, currently there are no endemicity classifications or elimination targets to monitor the effects of interventions. This study aimed at establishing case definitions and indicators that can be used to assess endemicity, elimination and clinical outcomes of podoconiosis.
Methods
This paper describes the result of a Delphi technique used among 28 experts. A questionnaire outlining possible case definitions, endemicity classifications, elimination targets and clinical outcomes was developed. The questionnaire was distributed to experts working on podoconiosis and other neglected tropical diseases in two rounds. The experts rated the importance of case definitions, endemic classifications, elimination targets and the clinical outcome measures. Median and mode were used to describe the central tendency of expert responses. The coefficient of variation was used to describe the dispersals of expert responses.
Results
Consensus on definitions and indicators for assessing endemicity, elimination and clinical outcomes of podoconiosis directed at policy makers and health workers was achieved following the two rounds of Delphi approach among the experts.
Conclusions
Based on the two Delphi rounds we discuss potential indicators and endemicity classification of this disabling disease, and the ongoing challenges to its elimination in countries with the highest prevalence. Consensus will help to increase effectiveness of podoconiosis elimination efforts and ensure comparability of outcome data.
doi:10.1093/inthealth/ihv043
PMCID: PMC4550552  PMID: 26185194
Delphi; Elephantiasis; Elimination; Endemicity; Non-filarial elephantiasis; Podoconiosis
9.  Effect of early and current Helicobacter pylori infection on the risk of anaemia in 6.5-year-old Ethiopian children 
BMC Infectious Diseases  2015;15:270.
Background
Epidemiological and clinical studies in high income countries have suggested that Helicobacter pylori (H. pylori) may cause anaemia, but evidence is lacking from low income countries.We examined associations between H. pylori infection in early childhood and anaemia at the age of 6.5 years in an Ethiopian birth cohort.
Methods
In 2011/12, 856 children (85.1 % of the 1006 original singletons in a population-based birth cohort) were followed up at age six and half. An interviewer-led questionnaire administered to mothers provided information on demographic and lifestyle variables. Haemoglobin level and red cell indices were examined using an automated haematological analyzer (Cell Dyn 1800, Abbott, USA), and stool samples analyzed for H. pylori antigen. The independent effects of H. pylori infection (measured at age 3.5 and 6.5 years) on anaemia, haemoglobin level, and red cell indices (measured at age 6.5 years) were determined using multiple logistic and linear regression.
Results
The prevalence of anemia was 34.8 % (257/739), and the mean (SD) haemoglobin concentration was 11.8 (1.1) gm/dl. Current H. pylori infection at age 6.5 years was positively, though not significantly related to prevalence of anaemia (adjusted OR, 95 % CI, 1.15; 0.69, 1.93, p = 0.59). Any H. pylori infection up to age 6.5 years was significantly associated with an increased risk of anaemia at age 6.5 (adjusted OR, 95 % CI, 1.68; 1.22, 2.32, p = 0.01). A significant reduction in haemoglobin concentration and red cell indices was also observed among children who had any H. pylori infection up to age 6.5 (Hb adjusted β = −0.19, 95 % CI, −0.35 to −0.03, p = 0.01; MCV adjusted β = −2.22, 95 % CI, −3.43 to −1.01, p = 0.01; MCH adjusted β = −0.63, 95 % CI, −1.15 to - 0.12, p = 0.01; and MCHC adjusted β = −0.67, 95 % CI, −1.21 to −0.14, p = 0.01), respectively.
Conclusion
This study provides further evidence from a low income country that any H. pylori infection up to age 6.5 is associated with higher prevalence of anaemia, and reduction of haemoglobin level and red cell indices at age 6.5.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-015-1012-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-015-1012-y
PMCID: PMC4501201  PMID: 26168784
Helicobacter pylori; Anaemia; Red cell indices; Birth cohort; Ethiopia
10.  Mental distress and podoconiosis in Northern Ethiopia: a comparative cross-sectional study 
International health  2014;7(1):16-25.
Background
The stigma, deformity and disability related to most neglected tropical diseases may lead to poor mental health. We aimed to assess the comorbidity of podoconiosis and mental distress.
Methods
A comparative cross-sectional study was conducted in 2012, including 346 people with podoconiosis and 349 healthy neighbourhood controls. Symptoms of mental distress were assessed using the validated Amharic translation of the Kessler-10 scale (K10). A linear regression analysis was conducted to identify factors associated with mental distress.
Results
The mean K10 score was 15.92 (95% CI: 15.27 to 16.57) in people with podoconiosis and 14.49 (95% CI: 13.85 to 15.12) in controls (average K10 scores 1.43 points higher [95% CI: 0.52 to 2.34]). In multivariate linear regression of K10 scores, the difference remained significant when adjusted for gender, income, alcohol use, age, place of residence and family history of mental illness. In the adjusted model, people with podoconiosis had K10 scores 1.37 points higher than controls (95% CI: 0.64 to 2.18). Other variables were also associated with high K10 scores: women had K10 scores 1.41 points higher than men (95% CI: 0.63 to 2.18). Those with family history of mental illness had K10 scores 3.56 points higher than those without (95% CI: 0.55 to 6.56).
Conclusions
This study documented a high burden of mental distress among people with podoconiosis compared with healthy controls. Taking this finding in the context of the high stigma and reduced quality of life, we recommend integration of psychosocial care into the current morbidity management of podoconiosis.
doi:10.1093/inthealth/ihu043
PMCID: PMC4236095  PMID: 25062906
Elephantiasis; Ethiopia; Mental distress; Mental health disorders; Neglected tropical disease; Podoconiosis
11.  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 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.
doi:10.4269/ajtmh.14-0446
PMCID: PMC4288951  PMID: 25404069
podoconiosis; mapping; non-filarial elephantiasis; lymphoedema; Ethiopia
12.  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.
doi:10.4269/ajtmh.14-0446
PMCID: PMC4288951  PMID: 25404069
13.  Association between Footwear Use and Neglected Tropical Diseases: A Systematic Review and Meta-Analysis 
Background
The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs.
Methodology
We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses.
Principal Findings
Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR = 0.15; 95% CI: 0.08–0.29), CLM (OR = 0.24; 95% CI: 0.06–0.96), tungiasis (OR = 0.42; 95% CI: 0.26–0.70), hookworm infection (OR = 0.48; 95% CI: 0.37–0.61), any STH infection (OR = 0.57; 95% CI: 0.39–0.84), strongyloidiasis (OR = 0.56; 95% CI: 0.38–0.83), and leptospirosis (OR = 0.59; 95% CI: 0.37–0.94). No significant association between footwear use and podoconiosis (OR = 0.63; 95% CI: 0.38–1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included.
Conclusions/Significance
Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination.
Protocol Registration
PROSPERO International prospective register of systematic reviews CRD42012003338
Author Summary
Consistent use of footwear may help in preventing or slowing down the progression of many neglected tropical diseases (NTDs). We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We found that footwear use reduces the risk of Buruli ulcer, tungiasis, hookworm, any STH infection, strongyloidiasis, and leptospirosis. No significant association between footwear use and podoconiosis was found and no data were available for mycetoma, myiasis or snakebite. We recommend that access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination.
doi:10.1371/journal.pntd.0003285
PMCID: PMC4230915  PMID: 25393620
14.  Extent of podoconiosis-related stigma in Wolaita Zone, Southern Ethiopia: a cross-sectional study 
SpringerPlus  2014;3:647.
Studies have indicated that social stigma related to podoconiosis (endemic non-filarial elephantiasis) has a major impact on the psychosocial wellbeing of patients. However, little effort has been made so far to quantify the level of both felt and enacted stigma in a range of domains of life. We used a recently developed podoconiosis stigma assessment scale to measure levels of stigma as recalled over the previous 12 months. One hundred and fifty patients with podoconiosis rated the levels of stigma they perceived and experienced in ‘interpersonal interactions’, ‘major life areas’ and ‘community, social and civic life’. High levels of stigma were observed on both felt and enacted stigma scales. The overall average stigma score was 40.7 (range 0 to 96). Enacted stigma was scored higher than felt stigma (mean score 21.2 vs. 19.5, respectively). The mean enacted stigma score was higher in ‘major life areas’, and ‘community, social and civic life’ than ‘interpersonal interactions’, while felt stigma was experienced most at the interpersonal level. Over half of patients reported that they had considered suicide in response to discrimination and prejudice, particularly in interpersonal interactions. Forced divorce, dissolution of marriage plan, insults and exclusion at social events were some of the most commonly mentioned forms of enacted stigma reported by affected individuals. Scores for overall level of stigma and enacted stigma increased significantly with stage of podoconiosis while the association observed in relation to felt stigma was only marginally significant (p = 0.085). Appropriate stigma reduction strategies must be identified and implemented in communities highly endemic for podoconiosis.
doi:10.1186/2193-1801-3-647
PMCID: PMC4233027  PMID: 25485190
Podoconiosis; Enacted stigma; Felt stigma; Ethiopia
15.  Perceptions of consent, permission structures and approaches to the community: a rapid ethical assessment performed in North West Cameroon 
BMC Public Health  2014;14:1026.
Background
Understanding local contextual factors is important when conducting international collaborative studies in low-income country settings. Rapid ethical assessment (a brief qualitative intervention designed to map the ethical terrain of a research setting prior to recruitment of participants), has been used in a range of research-naïve settings. We used rapid ethical assessment to explore ethical issues and challenges associated with approaching communities and gaining informed consent in North West Cameroon.
Methods
This qualitative study was carried out in two health districts in the North West Region of Cameroon between February and April 2012. Eleven focus group discussions (with a total of 107 participants) were carried out among adult community members, while 72 in-depth interviews included health workers, non-government organisation staff and local community leaders. Data were collected in English and pidgin, translated where necessary into English, transcribed and coded following themes.
Results
Many community members had some understanding of informed consent, probably through exposure to agricultural research in the past. Participants described a centralised permission-giving structure in their communities, though there was evidence of some subversion of these structures by the educated young and by women. Several acceptable routes for approaching the communities were outlined, all including the health centre and the Fon (traditional leader). The importance of time spent in sensitizing the community and explaining information was stressed.
Conclusions
Respondents held relatively sophisticated understanding of consent and were able to outline the structures of permission-giving in the community. Although the structures are unique to these communities, the role of certain trusted groups is common to several other communities in Kenya and Ethiopia explored using similar techniques. The information gained through Rapid Ethical Assessment will form an important guide for future studies in North West Cameroon.
doi:10.1186/1471-2458-14-1026
PMCID: PMC4195877  PMID: 25277694
16.  Integrated mapping of lymphatic filariasis and podoconiosis: lessons learnt from Ethiopia 
Parasites & Vectors  2014;7:397.
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.
Electronic supplementary material
The online version of this article (doi:10.1186/1756-3305-7-397) contains supplementary material, which is available to authorized users.
doi:10.1186/1756-3305-7-397
PMCID: PMC4153915  PMID: 25164687
Integrated; Mapping; Lymphedema; Elephantiasis; Lymphatic filariasis; Podoconiosis; Ethiopia
17.  Concerns about covert HIV testing are associated with delayed presentation of suspected malaria in Ethiopian children: a cross-sectional study 
Malaria Journal  2014;13:301.
Background
Early diagnosis is important in preventing mortality from malaria. The hypothesis that guardians’ fear of covert human immunodeficiency virus (HIV) testing delays presentation of children with suspected malaria was tested.
Methods
The study design is a cross-sectional survey. The study population consisted of guardians of children with suspected malaria who presented to health centres in Oromia Region, Ethiopia. Data were collected on attitudes to HIV testing and the duration of children’s symptoms using interview administered questionnaires.
Results
Some 830 individuals provided data representing a response rate of 99% of eligible participants. Of these, 423 (51%) guardians perceived that HIV testing was routinely done on blood donated for malaria diagnosis, and 353 (43%) were aware of community members who delayed seeking medical advice because of these concerns. Children whose guardians suspected that blood was covertly tested for HIV had longer median delay to presentation for evaluation at health centres compared to those children whose guardians did not hold this belief (three days compared to two days, p < 0.001). Children whose guardians were concerned about covert HIV testing were at a higher odds of a prolonged delay before being seen at a health centre (odds ratio 1.73, 95% confidence intervals: 1.10 to 270 for a delay of ≥3 days compared to those seen in ≤2 days).
Conclusion
Children whose guardians believed that covert testing for HIV was routine clinical practice presented later for investigation of suspected malaria. This may account for up to 14% of the delay in presentation and represents a reversible risk factor for suboptimal management of malaria.
doi:10.1186/1475-2875-13-301
PMCID: PMC4126071  PMID: 25098338
Malaria; HIV; Diagnosis; Delay; Stigma; Ethiopia
18.  Mental distress and podoconiosis in Northern Ethiopia: a comparative cross-sectional study 
International Health  2014;7(1):16-25.
Background
The stigma, deformity and disability related to most neglected tropical diseases may lead to poor mental health. We aimed to assess the comorbidity of podoconiosis and mental distress.
Methods
A comparative cross-sectional study was conducted in 2012, including 346 people with podoconiosis and 349 healthy neighbourhood controls. Symptoms of mental distress were assessed using the validated Amharic translation of the Kessler-10 scale (K10). A linear regression analysis was conducted to identify factors associated with mental distress.
Results
The mean K10 score was 15.92 (95% CI: 15.27 to 16.57) in people with podoconiosis and 14.49 (95% CI: 13.85 to 15.12) in controls (average K10 scores 1.43 points higher [95% CI: 0.52 to 2.34]). In multivariate linear regression of K10 scores, the difference remained significant when adjusted for gender, income, alcohol use, age, place of residence and family history of mental illness. In the adjusted model, people with podoconiosis had K10 scores 1.37 points higher than controls (95% CI: 0.64 to 2.18). Other variables were also associated with high K10 scores: women had K10 scores 1.41 points higher than men (95% CI: 0.63 to 2.18). Those with family history of mental illness had K10 scores 3.56 points higher than those without (95% CI: 0.55 to 6.56).
Conclusions
This study documented a high burden of mental distress among people with podoconiosis compared with healthy controls. Taking this finding in the context of the high stigma and reduced quality of life, we recommend integration of psychosocial care into the current morbidity management of podoconiosis.
doi:10.1093/inthealth/ihu043
PMCID: PMC4236095  PMID: 25062906
Elephantiasis; Ethiopia; Mental distress; Mental health disorders; Neglected tropical disease; Podoconiosis
19.  Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis 
Introduction
The precise trigger of podoconiosis — endemic non-filarial elephantiasis of the lower legs — is unknown. Epidemiological and ecological studies have linked the disease with barefoot exposure to red clay soils of volcanic origin. Histopathology investigations have demonstrated that silicon, aluminium, magnesium and iron are present in the lower limb lymph node macrophages of both patients and non-patients living barefoot on these clays. We studied the spatial variation (variations across an area) in podoconiosis prevalence and the associated environmental factors with a goal to better understanding the pathogenesis of podoconiosis.
Methods
Fieldwork was conducted from June 2011 to February 2013 in 12 kebeles (administrative units) in northern Ethiopia. Geo-located prevalence data and soil samples were collected and analysed along with secondary geological, topographic, meteorological and elevation data. Soil data were analysed for chemical composition, mineralogy and particle size, and were interpolated to provide spatially continuous information. Exploratory, spatial, univariate and multivariate regression analyses of podoconiosis prevalence were conducted in relation to primary (soil) and secondary (elevation, precipitation, and geology) covariates.
Results
Podoconiosis distribution showed spatial correlation with variation in elevation and precipitation. Exploratory analysis identified that phyllosilicate minerals, particularly clay (smectite and kaolinite) and mica groups, quartz (crystalline silica), iron oxide, and zirconium were associated with podoconiosis prevalence. The final multivariate model showed that the quantities of smectite (RR = 2.76, 95% CI: 1.35, 5.73; p = 0.007), quartz (RR = 1.16, 95% CI: 1.06, 1.26; p = 0.001) and mica (RR = 1.09, 95% CI: 1.05, 1.13; p < 0.001) in the soil had positive associations with podoconiosis prevalence.
Conclusions
More quantities of smectite, mica and quartz within the soil were associated with podoconiosis prevalence. Together with previous work indicating that these minerals may influence water absorption, potentiate infection and be toxic to human cells, the present findings suggest that these particles may play a role in the pathogenesis of podoconiosis and acute adenolymphangitis, a common cause of morbidity in podoconiosis patients.
doi:10.1186/1476-072X-13-24
PMCID: PMC4082615  PMID: 24946801
Podoconiosis; Spatial analysis; Epidemiology; Soil; Ethiopia
20.  Community-based survey of podoconiosis in Bedele Zuria woreda, west Ethiopia 
International Health  2013;5(2):119-125.
Background
Podoconiosis is a neglected tropical disease resulting in progressive bilateral swelling of the lower legs in barefoot individuals exposed to red-clay soil derived from volcanic rocks. It is a considerable public health problem in countries across tropical Africa, Central America and northern India. The present study aimed to assess the prevalence and clinical features of podoconiosis, and patients' experience of disease prevention and treatment, in Bedele Zuria woreda (district), west Ethiopia.
Methods
The study was conducted during 2011 and involved a house-to-house survey in all 2285 households of five randomly selected rural kebeles (villages).
Results
The prevalence of podoconiosis was 5.6% (379/6710) (95% CI 5.1–6.2%) and was significantly greater among women than men (6.6% vs 4.7%; p = 0.001). A total of 311 (16.9%) households had at least one member with podoconiosis, and 128 (33.8%) study participants reported having a blood relative with podoconiosis. Two hundred and forty-three (76.4%) podoconiosis patients were in the economically productive age group of 15–64 years. On average, a patient experienced at least six episodes of adenolymphangitis per year resulting in a loss of 25 working days per year.
Conclusion
This study has revealed a high burden of podoconiosis in west Ethiopia, and suggests that disease prevention and treatment programmes are needed.
doi:10.1093/inthealth/iht003
PMCID: PMC3889643  PMID: 24030111
Podoconiosis; Non-filarial elephantiasis; Lymphoedema; Prevalence; Survey; Ethiopia
21.  A mixed-methods study on perceptions towards use of Rapid Ethical Assessment to improve informed consent processes for health research in a low-income setting 
BMC Medical Ethics  2014;15:35.
Background
Rapid Ethical Assessment (REA) is a form of rapid ethnographic assessment conducted at the beginning of research project to guide the consent process with the objective of reconciling universal ethical guidance with specific research contexts. The current study is conducted to assess the perceived relevance of introducing REA as a mainstream tool in Ethiopia.
Methods
Mixed methods research using a sequential explanatory approach was conducted from July to September 2012, including 241 cross-sectional, self-administered and 19 qualitative, in-depth interviews among health researchers and regulators including ethics committee members in Ethiopian health research institutions and universities.
Results
In their evaluation of the consent process, only 40.2% thought that the consent process and information given were adequately understood by study participants; 84.6% claimed they were not satisfied with the current consent process and 85.5% thought the best interests of study participants were not adequately considered. Commonly mentioned consent-related problems included lack of clarity (48.1%), inadequate information (34%), language barriers (28.2%), cultural differences (27.4%), undue expectations (26.6%) and power imbalances (20.7%). About 95.4% believed that consent should be contextualized to the study setting and 39.4% thought REA would be an appropriate approach to improve the perceived problems. Qualitative findings helped to further explore the gaps identified in the quantitative findings and to map-out concerns related to the current research consent process in Ethiopia. Suggestions included, conducting REA during the pre-test (pilot) phase of studies when applicable. The need for clear guidance for researchers on issues such as when and how to apply the REA tools was stressed.
Conclusion
The study findings clearly indicated that there are perceived to be correctable gaps in the consent process of medical research in Ethiopia. REA is considered relevant by researchers and stakeholders to address these gaps. Exploring further the feasibility and applicability of REA is recommended.
doi:10.1186/1472-6939-15-35
PMCID: PMC4055294  PMID: 24885049
Rapid ethical assessment; Ethiopia; Research ethics; Consent
22.  Effects of Early Life Paracetamol Use on the Incidence of Allergic Disease and Sensitization: 5 Year Follow-Up of an Ethiopian Birth Cohort 
PLoS ONE  2014;9(4):e93869.
Introduction
The hypothesis that paracetamol, one of the most widely used medicines, may increase the risk of asthma and allergic disease is of obvious importance but prospective cohort data looking at dose and timing of exposure are lacking.
Objective
The aim of the study is to investigate the role of paracetamol use in early life on the prevalence and incidence of wheeze, eczema, rhinitis and allergic sensitization, prospectively over 5 years in an Ethiopian birth cohort.
Methods
In 2005/6 a birth cohort of 1006 newborns was established in Butajira, Ethiopia. Questionnaire data on allergic disease symptoms, paracetamol use and numerous potential confounders were collected at ages 1, 3 and 5, and allergen skin sensitivity measured at ages 3 and 5. Multivariate logistic regression was used to determine independent effects of paracetamol exposure on the incidence of each outcome between ages 3 and 5, and prevalence at age 5.
Findings
Paracetamol use in the first 3 years of life was reported in 60% of children and was associated with increased incidence of wheeze, eczema, rhinitis and allergic sensitisation between ages 3 and 5 which was statistically significant for wheeze and eczema. High exposure (reported use in the past month at age 1 and 3) was associated with a more than 3-fold increased risk of new onset wheeze (adjusted odds ratio (OR) 3.64; 95% confidence interval, 1.34 to 9.90) compared to never users. Use in the past year at age 3 but not age 1 was associated with ORs at least as large as those for use in first year of life only. Significant positive dose-response effects of early life use were seen in relation to the prevalence of all outcomes at age 5.
Conclusions
Use of paracetamol in early life is a strong risk factor for incident allergic disease in childhood.
doi:10.1371/journal.pone.0093869
PMCID: PMC3981735  PMID: 24718577
23.  Stigma towards a Neglected Tropical Disease: Felt and enacted Stigma Scores among Podoconiosis Patients in Northern Ethiopia 
BMC Public Health  2013;13:1178.
Background
Podoconiosis, or non-filarial elephantiasis, is a neglected tropical disease (NTD) characterised by swelling of the lower legs. When left untreated, this disfiguring condition has a significant social impact. This study aimed to describe the stigma experience among podoconiosis patients in Dembecha, Northern Ethiopia and assess potential associations between stigma and sociodemographic determinants.
Methods
The study was conducted in May 2012 in Northern Ethiopia. A questionnaire-based cross-sectional study design was used and stigma was assessed using a validated podoconiosis stigma scale including 'felt’ and 'enacted’ stigma domains. Enacted stigma includes the experience of discrimination such as abuse, loss of employment or prejudicial attitudes, while felt stigma is the perceived fear of enacted stigma. A multivariable linear regression model was used to explore determinants that may be associated with stigma.
Results
A total of 346 clinically confirmed podoconiosis patients participated in the study. The total mean score of all stigma scale items was 30.7 (Range = 0 to 96). There was a higher mean score of scale items in domains of felt stigma (21.7; Range = 0 to 45) as compared to enacted stigma (9.0; Range = 0 to 51). The total mean score of all stigma scale items appeared to increase with disease stage. A final adjusted linear regression model found an association between stigma and factors including monthly income, duration lived in the current residence, and disease stage, after controlling for confounders.
Conclusion
Podoconiosis is a stigmatized disease with a clear social impact. This paper documented the burden of podoconiosis-related stigma and identified associated factors. Programs aimed at preventing and treating podoconiosis should incorporate interventions to mitigate both felt and enacted stigma. Interventions targeting patients should prioritize those with advanced disease.
doi:10.1186/1471-2458-13-1178
PMCID: PMC3878751  PMID: 24330684
Podoconiosis; Stigma; Discrimination; NTD; Ethiopia
24.  Individual Correlates of Podoconiosis in Areas of Varying Endemicity: A Case-Control Study 
Background
Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls.
Methods/principal findings
This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: ‘low’ (prevalence <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.
Author Summary
Podoconiosis is a neglected tropical disease that results in swelling of the lower legs and feet. It is common among barefoot individuals within defined areas due to the geochemical characteristics of the soil in these areas. Presence of podoconiosis and its huge burden among the affected people in north Ethiopia has previously been documented. Moreover, difference in the occurrence of the disease by area and among individuals had been observed. In the present study, we investigated individual factors for the occurrence of podoconiosis, by comparing individuals with podoconiosis and without podoconiosis that live in three areas with varying disease prevalence. We found that individuals with the disease, particularly women, were less educated, with lower income and less likely to be married, compared to healthy individuals. Moreover, more than one individual was found in most of the affected households. Podoconiosis-affected individuals started wearing shoes at later ages than healthy individuals, and their feet were observed to be more cracked and dirty. There is a recent increase in shoe-wearing among all study subjects. We concluded that intervention efforts should focus to address late age shoe-wearing and inequalities in education, income and marriage, between podoconiosis affected individuals, and particularly among female patients. In addition, the presence of more than one patient per household helps for targeted case identification for intervention.
doi:10.1371/journal.pntd.0002554
PMCID: PMC3854961  PMID: 24340109

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