Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population.
A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016. Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio-demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract.
A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio OR 1.57 (95% CI 1.02–2.40), p = 0.04. There was no significant difference in prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55–1.25), p = 0.36. Mean best visual acuity was 0.59 (SD 0.06) in podoconiosis cases compared to 0.44 (SD 0.04) in controls, p<0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08–6.39), P = 0.03.
Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial.
Podoconiosis is an NTD causing chronic leg swelling in subsistence farming communities in the tropics. There is no research on the association between podoconiosis and two common causes of blindness and visual impairment; trachomatous trichiasis (TT) and cataract. TT is the blinding consequence of conjunctival scarring in trachoma, the leading infectious cause of blindness globally. Cataract is an age-related disease of the lens and remains the leading cause of visual impairment worldwide. Both podoconiosis and TT are NTDs endemic to Ethiopia and promote poverty through many factors such as disability, reduced economic productivity and stigma. This comparative cross-sectional study explored the association between podoconiosis and these two eye diseases. We found that podoconiosis patients were burdened with higher levels of blindness and low vision, had higher prevalence of TT and more severe cataract than their matched neighbourhood controls. These findings can help to direct an integrated approach to managing these two NTDs (podoconiosis and TT) and trigger further research in to the wider context of the double burden of eye disease and NTDs.
Citation: Burn H, Aweke S, Wondie T, Habtamu E, Deribe K, Rajak S, et al. (2017) Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: A comparative cross sectional study. PLoS Negl Trop Dis 11(2): e0005388. https://doi.org/10.1371/journal.pntd.0005388
Editor: Christine M. Budke, Texas A&M University College Station, UNITED STATES
Received: September 20, 2016; Accepted: February 4, 2017; Published: February 10, 2017
Copyright: © 2017 Burn 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.
Data Availability: All relevant data are within the Supporting Information files.
Funding: This work was funded by The Association of Physicians Great Britain and Ireland; Links With Developing Countries Grant, https://theassociationofphysicians.org.uk/index.php/links-with-developing-countries. KD is funded by Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine [grant number 201900/Z 16/Z]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Neglected tropical diseases (NTDs) do not occur in isolation but have substantial geographical overlap. This results in an increased burden of co-morbidity within a population, commonly leading to individuals suffering from one or more NTDs. These conditions share common risk factors including lack of access to clean water, sanitation and hygiene practices. We describe here a study in which we aimed to explore the association between the NTD podoconiosis and two common eye diseases; one an NTD (trachomatous trichiasis) and another a common age-related disabling eye disease (cataract), within a rural population in northern Ethiopia.
Podoconiosis is a non-filarial elephantiasis that predominantly affects subsistent farmers in areas of red clay soil covered highlands of tropical Africa, Northern India and South and Central America [3,4,5,6]. It causes painful swelling and deformity of the lower legs with acute, painful inflammatory events known as acute adenolymphangioadenitis (ALA) . Although the aetiology is not fully understood, current evidence suggests it occurs as a result of both a genetic susceptibility and exposure to irritant mineral particles in volcanic soils [7,8,9,10]. The disease carries a high socio-economic burden and is highly stigmatizing [11,12,13]. Nationwide mapping in 2015 found podoconiosis to be endemic in 345 districts in Ethiopia with a prevalence of 4% . East Gojam zone in Amhara region, where this study took place, has a podoconiosis prevalence of 3.3% . The recommended management of podoconiosis is inexpensive and simple involving foot hygiene, emollient, bandaging, exercise and wearing socks and shoes .
Anecdotally clinicians and researchers working with populations affected by podoconiosis report a high prevalence of cataract and trachomatous trichiasis (TT) among affected individuals.
The 2006 National Blindness Survey of Ethiopia found the prevalence of blindness and low vision in Amhara to be 1.4% and 4.9%, respectively Nationwide, cataract and trachomatous corneal opacity were found to be the leading causes of blindness with cataract accounting for 49.9% and trachomatous corneal opacity 11.5% .
Cataract is a clouding of the lens, which results in decreased vision. The leading cause is age. Cataract develops at a younger age in tropical and poor countries. The precise reasons for this are unclear but it is likely to be due to a combination of factors including episodes of dehydration in early life, diet, and solar and heat radiation .
Trachoma is the leading infectious cause of blindness worldwide . The disease starts in childhood with recurrent infection of the tarsal conjunctiva by Chlamydia trachomatis producing chronic inflammation. This leads to tarsal scarring followed by entropion (inward rotation of the eyelid) and trichiasis, a painful condition where eyelashes rub on the cornea causing corneal scarring.
Ethiopia is one of the most trachoma-affected countries in the world; in 2016 nearly 50% of people at risk of trachoma globally live in Ethiopia, Malawi and Nigeria . The number of people with TT awaiting surgery in 2016 is 693,000, again the largest in the world . The 2006 survey found Amhara Regional State bears an estimated 45% of the national trichiasis burden with approximately one in twenty of all adults suffering from the condition. Since 2001 TT surgery has been provided by the Amhara Regional Trachoma Control Programme with health workers throughout Amhara Region trained to perform TT surgery, including 40 in East Gojam Zone.
Ethiopia carries a high burden of Neglected Tropical Diseases, and is estimated to have the highest burden of podoconiosis and trachoma in Sub-Saharan Africa . Both podoconiosis and trachoma are part of the Ethiopian Government’s National Neglected Tropical Disease (NTD) Master Plan . Launched in 2013, the NTD Master Plan pledged to achieve WHO NTD elimination and control targets by 2020. Evidence of the presence of the double burden of podoconiosis and TT will facilitate decisions on the integration of policy and treatment programmes for these two NTDs.
Study setting and design
A comparative cross-sectional study was carried out in East Gojam Zone, Amhara Region, Ethiopia during four weeks in May 2016. Amhara is one of 9 regions and 2 city administrations of Ethiopia and is divided into 10 zones. East Gojam zone is divided into 20 woredas (equivalent of districts), which are divided into kebeles (the lowest governmental administrative unit). Within East Gojam Zone the Woreda Enarj Enawga was selected for this study as it was known to have a high burden of podoconiosis and access to recent complete data from the Podoconiosis Burden Assessment 2015 . Enarj Enawga has a population of 167,402, of which 92% are rural inhabitants . A non-random convenience sampling method was used to select 12 kebeles within Enarj Enwarga based on geographical location and accessibility.
Assuming the prevalence of cataract in healthy controls is 8% and the effect estimate is an odds ratio of 2, we calculated the need to recruit 336 cases and 336 cases for 80% power and 5% significance .
Study population and sampling procedure
Cases were located using the Podoconiosis Burden Assessment 2015 which provided participant name, household name, and village for all individuals over the age of 40 with podoconiosis within each kebele . Every podoconiosis case over age 40 within each of the 12 kebeles was invited to take part in the study. In total, 460 podoconiosis cases were identified. They were invited to participate in the study through both verbal information via the Kebele Leader and a written letter of invitation asking them to attend a health centre on a particular date.
Neighbourhood controls matched by age (+/- 5 years), sex and village were selected randomly from a residents’ register detailing each individual living within each village. Village leaders, Health Extension Workers and kebele leaders were able to locate each control selected. All were provided with information about the study and invited by letter to attend a health centre within their kebele on a particular date. Controls were excluded if they were under 40 years old, had podoconiosis on clinical examination, or had a first-degree relative with podoconiosis.
Measurement and data collection
The primary outcomes for participants with podoconiosis and healthy neighbourhood controls were: 1) presence of cataract 2) presence of TT.
Secondary outcomes were: grade of cataract, severity of TT, visual acuity, socio-demographic variables (age, sex, occupation), socio-economic status, history of hypertension, history of diabetes, previous eye surgery, previous eye trauma, previous eye diagnosis, number of acute podoconiosis attacks and stage of podoconiosis.
Data were collected through an interview-administered questionnaire followed by clinical examination. Questionnaires were administered by trained Amharic-speaking data collectors. Visual acuity was tested using PEEK Visual Acuity on smartphones recorded on a LogMar scale . LogMAR values were categorised according to the ICD-10 classification of visual impairment; normal vision, ≤ 0.4; mild impairment, 0.4–1.0; severe impairment, 1.0–1.3; blindness ≥1.3 . In this study we present only best unaided vision as no patients had spectacles for distance correction. Podoconiosis grading involved examination of both legs using a validated 5 stage grading system carried out by a local Podoconiosis Nurse Specialist . An ophthalmic officer and a medical doctor carried out the clinical eye examinations. Tropicamide 1.0% mydriatic drops were administered to both eyes. Cataract was examined using a direct ophthalmoscope at 30cm from dilated pupils as slit lamp examination was unavailable. Cataract was classified into five grades according to Mehra and Minassian’s method of grading in eye surveys using degree of opacity in the red reflex to define the grade . Grades 4 and 5 were regarded as severe matured cataract requiring surgery. Both eyes were then examined using a torch and x2.5 magnifying binocular loop for signs of trachoma. Each eye was examined for in-turned lashes (TT), the cornea inspected for central corneal opacities (opacities within central 4mm) and the upper conjunctiva everted and examined for inflammation (Trachomatous Inflammation—Follicular (TF) and Trachomatous Inflammation—Intense (TI)) and scarring (Trachomatous Scarring (TS)). The WHO simplified trachoma grading system was used to define each of these stages . TT was defined as one or more lashes touching the globe or evidence of eyelash epilation . Severity of TT was recorded by counting the number of lashes touching the globe when looking straight ahead and subdivided into corneal lashes (touching cornea) or peripheral lashes (touching medial or lateral conjunctiva). TT severity was classified into two groups: major as >5 peripheral or corneal lashes and minor as <6 peripheral or corneal lashes. Patients were told the findings of the eye examination at the end of the study. Individuals with signs of active trachoma (TF and/or TI) were offered treatment with 1% tetracycline eye ointment. TT patients were referred to health centres where free TT surgery was available. Patients with grade 4 or 5 cataract were referred to Debre Markos Hospital for cataract surgery. All podoconiosis patients were counseled by a Podoconiosis Specialist Nurse for podoconiosis management and enrolled into existing podoconiosis clinics.
Data were coded, entered, cleaned and analysed using IBM SPSS Statistics version 22. Descriptive analysis of the socio-demographic and clinical characteristics of cases and controls was performed. When comparing simple frequencies, the χ2 test was used to establish significance. Means were compared using the independent t-test. Principal Components Analysis was used to reduce 15 wealth index factors (gained from the interview-administered questionnaire) into three household index values taking the first component as a measure of economic status divided into three categories: poor, middle class and wealthy [30,31]. A logistic regression model was used to determine the clinical and socio-demographic correlates of trachomatous trichiasis and cataract. The model was used to measure the association between podoconiosis and these two eye diseases (cataract and TT) adjusting for sex, age, occupation and socio-economic status. These confounding factors were chosen prior to data collection. They were chosen as factors likely to influence the association between podoconiosis and these two eye diseases based on previous literature [32,33,34,35,42].
Ethical approval was gained from Amhara Regional Health Bureau and the Research Governance & Ethics Committee of Brighton & Sussex Medical School. An Amharic-speaking study supervisor gave, to each of the participants, an introduction to the study and the reasons why it was being conducted. Then, all participants were given written information in Amharic outlining the reason for the study and what would be involved if they chose to participate. If participants were unable to read or write, the information sheet was read to them individually. Informed consent was gained by signature and a thumbprint was used if the participant was unable to write . The consent was then countersigned by an independent witness. Study participants identified with ocular disease or podoconiosis were managed as per local protocol. A podoconiosis nurse was present throughout the study to provide education regarding podoconiosis treatment and integration into existing clinics.
A total of 700 participants were included in this study: 350 podoconiosis cases and 350 healthy neighbourhood controls. The socio-demographic characteristics of cases and controls are described in Table 1. More cases (60.3%) and controls (62.6%) were male than female. The mean age distribution between cases and controls was similar at 57 and 56 years respectively. The great majority of both cases and controls were rural farmers and married. However, compared to their neighbourhood controls, significantly larger numbers of podoconiosis cases were either divorced or widowed; 102 (29.2%) vs 56 (16.0%), p = 0.001, and lived in poorer households; 146 (41.7%) vs 88 (25.1%); p<0.001.
Over half of all podoconiosis patients had a first-degree relative with podoconiosis and had experienced an acute attack in the past 30 days. The median stage of podoconiosis for both legs was stage 2 (defined as persistent below knee swelling) . The clinical characteristics of cases and controls are described in Table 2. Few patients in either group had a history of hypertension and diabetes. Compared to the controls, a significantly higher proportion of podoconiosis cases had an ocular problem; 52 (14.9%) vs 86 (24.6%), p = 0.001, and had had eye surgery; 49 (14.0%) vs 75 (21.4%); p = 0.01. In particular, compared to controls, a higher proportion of podoconiosis cases had had TT surgery (61 (17.4%) in cases vs 42 (12.0%) in controls, p = 0.04), a diagnosis of TT (62 (17.7%) in cases vs 40 (11.4%) in controls, p = 0.03) or a diagnosis of cataract (16 (4.6%) in cases vs 6(1.7%) in controls, p = 0.02).
Podoconiosis patients were found to have significantly lower visual acuity than healthy controls. (Table 3). Mean best visual acuity was 0.59 (SD 0.06) in podoconiosis cases compared to 0.44 (SD 0.04) in controls, p<0.001. The proportion of patients classified as blind was significantly higher in the podoconiosis group; 5.6% vs 2.0%; OR 2.97 (95% CI 1.24–7.11), p = 0.02. When adjusted for age, sex and socioeconomic status the association remained significant; adjusted OR 2.63 (1.08–6.39), p = 0.03.
TT and cataract prevalence among cases and controls
The prevalence of TT was higher in cases (65, 18.6%) than controls (43, 12.3%); OR 1.63; (95% CI 1.07–2.47), p = 0.02. 13 out of 65 (20%) cases had major trichiasis compared to 5 out of 43 (11%) of healthy controls (p = 0.16). The odds of having TT remain significantly greater for individuals with podoconiosis after adjustment for age, sex, occupation, socio-economic status and distance from water; adjusted OR 1.57 (95% CI 1.02–2.40), p = 0.04. Female patients had greater odds of TT compared to male patients OR 1.58 (95% CI 1.38–1.77), p<0.001 (Table 4).
No significant difference in cataract prevalence was found between the two groups; 272 (77.7%) vs 286, (81.7%), OR, 0.87; (95% CI, 0.59–1.26), p = 0.47. However, podoconiosis cases were shown to have more severe cataract. The number of patients with grade 4 or 5 cataract in either eye or both was 37 (10.6%) for cases vs 29 (8.6%) for controls (p = 0.01). Many more eyes in the podoconiosis case group could not be examined due to severe corneal opacity or phthisis; 43 out 700 (6.1%) compared with 14 out of 700 (2%). The odds of having cataract were not affected by the presence of podoconiosis; adjusted OR 0.83 (95% CI 0.55–1.25), p = 0.36, and only significantly associated with age with an adjusted odds ratio of 1.07 (95% CI 1.05–1.09), p = 0.001 (Table 5).
The study found that podoconiosis patients have worse visual acuity than healthy neighbourhood controls, with many more podoconiosis patients classified as blind. The prevalence of TT causing low vision through corneal opacification is higher in podoconiosis patients, creating a double burden of neglected tropical disease in this population. No significant difference in the prevalence of cataract was observed between podoconiosis patients and controls, however a higher number of podoconiosis cases had dense cataract (grade 4 or 5) and previous cataract surgery when compared to their neighbourhood controls.
NTDs commonly overlap within a population. Indeed, 80 million people in Ethiopia live in areas where one or more NTDs co-exist. Mapping of NTDs in Ethiopia has shown much geographical overlap between podoconiosis and other NTDs. For example Nationwide mapping has shown that 29 districts in Ethiopia are co-endemic for LF and podoconiosis, 116 co-endemic for onchocerciasis and podoconiosis, 302 co-endemic for trachoma and podoconiosis, 342 co-endemic for SHT and podoconiosis . However, little is known regarding the overlap of NTDs within individuals. One study showed an overlap between Soil Transmitted Helminth (STH) infection and podoconiosis . The authors concluded that this was likely to be a result of barefoot practices predisposing the individual to both diseases, rather than a shared biological mechanism. The association between the two NTDs podoconiosis and TT can be hypothesised to be the result of both shared environmental risk factors and a common biological pathology.
It is known that NTDs often co-exist within a population due to shared environmental risk factors such as sanitation, hygiene, poverty and access to health care [2,39]. The management of both trachoma and podoconiosis share common hygiene messages; for example, trachoma elimination programmes have focused on promoting facial cleanliness, while podoconiosis programmes educate patients about regular foot washing practices [41,16]. Both diseases are associated with reduced availability of water, sanitation and hygiene (WASH) facilities.40 Similarly, both diseases have been linked to poverty [42,14]. In this study podoconiosis patients were found to be significantly poorer than their neighbourhood controls, as we would expect from previous studies . Likewise, trachoma is widely considered a disease of poverty .
Podoconiosis has a social impact and this in turn may lead to an increased burden of eye disease, independent of an association with trachoma . Alongside economic poverty, individuals with podoconiosis are marginalised and stigmatised within their societies, leading to reduced living standards in comparison to their healthy neighbours [11,14]. Marginalisation within society alongside poor living standards among individuals living with podoconiosis may predispose to eye disease and reduced visual acuity through affecting health seeking behaviour , attendance for surgical procedures and disease prevention awareness.
Alongside an environmental and socio-economic hypothesis, it is possible that the association between podoconiosis and TT is also a result of shared biological pathology in these two chronic, scarring inflammatory diseases [44,45]. Previous research investigating pro-inflammatory and pro-fibrotic markers in serum and HLA associations in these two diseases could provide some insight into a potential shared pathology ., To date, very few studies have investigated the systemic effects of podoconiosis. Bilateral leg lymphoedema is thought to be caused by elements common in irritant volcanic soils (eg. aluminium, silicon, magnesium and iron) being absorbed through the foot and entering lower limb lymph nodes [46,7,10,47,48]. While it is the foot which facilitates dermal absorption, it is possible that these irritant elements cause wider systemic inflammatory effects. Addisu et al  compared levels of oxidative stress biomarkers in podoconiosis patients and healthy controls and found higher levels of these biomarkers in the serum of podoconiosis patients, suggesting inflammation in the early stage of the disease. Burton et al studied progressive trachomatous conjunctival scarring in an Ethiopian and Tanzanian cohort. They found that scarring progressed over a two year period in the absence of C. trachomatis . Progressive scarring was associated with mucosal inflammation with an increased association in individuals with more frequent inflammatory episodes. This chronic conjunctival inflammation was associated with increased expression of pro-inflammatory factors and extracellular matrix regulators systemically including the pro-fibrotic factor CTGF, closely associated with TGFβ. Both podoconiosis and progressive trachomatous scarring have been associated with altered levels of pro-inflammatory factors in the serum. It is possible that systemic inflammation in podoconiosis patients could provide an initial hypothesis to explain the increased levels of trachomatous inflammation, trachomatous scarring and trachomatous trichiasis among podoconiosis cases. Further studies viewing podoconiosis as a systemic disease are required to investigate further potential effects of chronic systemic inflammation in these patients.
Many individuals who come into contact with irritant volcanic soils do not go on to develop podoconiosis [46,49]. Similarly, the natural history of trachoma varies significantly in prevalence and severity between families and communities with shared environmental risk factors . The gene-environment interaction for both these diseases has been investigated, including the frequency of HLA antigens in both podoconiosis and blinding trachoma. Both podoconiosis and trachoma are associated with HLA Class II suggesting both are T cell mediated inflammatory diseases [8,51]. A shared pathogenesis associated with HLA Class II may account for some of the association between these two NTDs.
Both podoconiosis and TT have been shown to worsen poverty, reduce quality of life and increase the burden of disability in predominately poor rural communities [52,53,54,55,56]. Understanding that individuals can be burdened with both diseases could reduce the disease-specific approach to management and lead to an integrated management of these two NTDs at different levels. Firstly, the screening and diagnosis of these diseases could combine using the same community based health extension worker led household screening that is seen in trichiasis screening in Amhara region, Ethiopia. Both are highly visible diseases making community based screening very effective. Secondly, integrated treatment approaches could focus on common hygiene messages among the two groups and a focus on the improvement of WASH facilities, a key element of NTD management projects globally .
A key limitation of this study is the absence of a detailed slit lamp ophthalmic examination of the anterior segment and retina of the eye. While we found that TT is more common in this population, we were unable to study the prevalence of other eye diseases that could also account for the reduced vision in podoconiosis patients. Examining for cataract using direct ophthalmoscopy rather than slit lamp risks missing certain types of cataract, in particular nuclear cataract. A further limitation is the possibility of selection bias. While 460 podoconiosis patients were invited to take part, there was a high attrition rate before enrolment in the study with only 350 enrolling. Those with more disabling podoconiosis or worse vision may have been less likely to attend the local health facilities due to difficulties of travel. Lastly, the study only took place in one small rural population of northern Ethiopia reducing the generalizability of results to other populations affected by podoconiosis, trachoma and cataract.
We conclude that podoconiosis patients have a greater burden of visual impairment than individuals living in the same neighbourhood without the disease. They are more likely to suffer from TT, and other stages of trachoma. Podoconiosis patients are poorer than their neighbours without the disease, but this alone may not be enough to account for this association and the significant difference in their burden of poor vision and blindness. Alongside shared environmental risk factors, shared biological mechanisms between these two NTDs, podoconiosis and TT, may contribute to the association that has been found and warrants further research to gain a better understanding of their co-endemicity. In particular, a focus in the future of studying and managing these two diseases together may help to reduce their burden in this northern Ethiopian population and farther afield.
We would like to thank Tsige Amberbir and Abebe Kelemework for their logistical support during data collection in Amhara.
- Conceptualization: HB SR GD EH.
- Data curation: TW SA HB.
- Formal analysis: HB EH SR GD SB KD.
- Funding acquisition: HB GD.
- Investigation: HB TW SA.
- Methodology: HB TW SA EH SR.
- Project administration: GD HB.
- Resources: TW SA EH.
- Supervision: GD.
- Validation: HB TW SA.
- Visualization: HB.
- Writing – original draft: HB.
- Writing – review & editing: KD GD EH SR SB HB.
- 1. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Sachs SE, Sachs JD. Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria. PLOS Med. 2006 Jan 31;3(5):e102. pmid:16435908
- 2. Water, Sanitation and Hygiene for accelerating and sustaining progress on Neglected Tropical Diseases: A Global Strategy 2015–2020. World Health Organisation.
- 3. Onapa AW, Simonsen PE, Pedersen EM. Non-filarial elephantiasis in the Mt. Elgon area (Kapchorwa District) of Uganda. Acta Trop. 2001 Feb 23;78(2):171–6. pmid:11230827
- 4. Ruiz L, Campo E, Corachán M. Elephantiasis in São Tomé and Príncipe. Acta Trop. 1994 Jun;57(1):29–34. pmid:7942352
- 5. Price E.W., 1976. Endemic elephantiasis of the lower legs in Rwanda and Burundi. Trop. Geog. Med 28, 283–290.
- 6. Tada M.S., Marsden P.D., 1993. Probable podoconiosis in Brasilia. Rev Soc Bras. Med. Trop. 26, 255 pmid:8159829
- 7. Price EW. The association of endemic elephantiasis of the lower legs in East Africa with soil derived from volcanic rocks. Trans R Soc Trop Med Hyg. 1976;70(4):288–95. pmid:1006757
- 8. Ayele F, Adeyemo A, Finan C, Hailu E, Sinnott P, Burlinson ND, et al. HLA Class II Locus and Susceptibility to Podoconiosis. New England Journal of Medicine. 2012 Mar 29;366(13):1200–8. pmid:22455414
- 9. Davey G. Podoconiosis, non-filarial elephantiasis, and lymphology. lymphology. 2010 Dec;43(4):168–77. pmid:21446572
- 10. Davey G, Newport M. Podoconiosis: the most neglected tropical disease? Lancet. 2007 Mar 17;369(9565):888–9. pmid:17368134
- 11. Deribe K, Tomczyk S, Mousley E, Tamiru A, Davey G. Stigma towards a neglected tropical disease: felt and enacted stigma scores among podoconiosis patients in Northern Ethiopia. BMC Public Health. 2013;13:1178. pmid:24330684
- 12. Tora A, Davey G, Tadele G. A qualitative study on stigma and coping strategies of patients with podoconiosis in Wolaita zone, Southern Ethiopia. Int Health. 2011 Sep;3(3):176–81. pmid:24038367
- 13. Tekola F, Mariam DH, Davey G. Economic costs of endemic non-filarial elephantiasis in Wolaita Zone, Ethiopia. Tropical Medicine & International Health. 2006 Jul 1;11(7):1136–44.
- 14. Deribe K, Brooker SJ, Pullan RL, Sime H, Gebretsadik A, Assefa A, et al. Epidemiology and Individual, Household and Geographical Risk Factors of Podoconiosis in Ethiopia: Results from the First Nationwide Mapping. Am J Trop Med Hyg. 2015 Jan 7;92(1):148–58. pmid:25404069
- 15. Molla YB, Tomczyk S, Amberbir T, Tamiru A, Davey G. Podoconiosis in East and West Gojam Zones, northern Ethiopia. PLoS Negl Trop Dis. 2012;6(7):e1744. pmid:22816005
- 16. Sikorski C, Ashine M, Zeleke Z, Davey G. Effectiveness of a simple lymphoedema treatment regimen in podoconiosis management in southern ethiopia: one year follow-up. PLoS Negl Trop Dis. 2010;4(11):e902. pmid:21152059
- 17. Burton MJ, Mabey DCW. The Global Burden of Trachoma: A Review. PLOS Negl Trop Dis. 2009 Oct 27;3(10):e460. pmid:19859534
- 18. Rajak S, Sandford-Smith J. Eye Diseases in Hot Climates. Fifth Edition. JP Medical. 2015.
- 19. Berhane Y, Worku A, Bejiga A (2006) National Survey on Blindness, Low Vision and Trachoma in Ethiopia. Addis Ababa: Addis Ababa: Ministry of Health.
- 20. Eliminating Trachoma: Accelerating Towards 2020. WHO Alliance for elimination of Trachoma by 2020. 2016
- 21. Deribe K, Meribo K, Gebre T, Hailu A, Ali A, Aseffa A, et al. The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination. Parasite Vectors. 2012;5:240.
- 22. Federal Democratic Republic of Ethiopia Ministry of Health. National Master Plan for Neglected Tropical Diseases (NTDs) 2013–2015. June 2013.
- 23. National Podoconiosis Action Network. Burden assessment of podoconiosis and lymphatic filariasis in selected districts of Ethiopia. 2015 Addis Ababa, Ethiopia.
- 24. The Central Statistics Agency of Ethiopia; 2007 National Consensus
- 25. Bastawrous A, Rono HK, Livingstone IT, et al. Development and validation of a smartphone-based visual acuity test (peek acuity) for clinical practice and community-based fieldwork. JAMA Ophthalmol. 2015 Aug 1;133(8):930–7. pmid:26022921
- 26. International Statistical Classification of Diseases and Related Health Problems. 10th Revision. WHO.
- 27. Tekola F, Ayele Z, HaileMariam D, Fuller C, Davey G. Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis). Trop Med Int Health. 2008 Oct;13(10):1277–83. pmid:18721188
- 28. Mehra V, Minassian DC. A rapid method of grading cataract in epidemiological studies and eye surveys. Br J Ophthalmol. 1988 Nov;72(11):801–3. pmid:3207653
- 29. WHO simplified trachoma grading system. Community Eye Health. 2004;17(52):68. pmid:17491830
- 30. Vyas S, Kumaranayake L. Constructing socio-economic status indices: how to use principal components analysis. Health Policy Plan. 2006 Nov 1;21(6):459–68. pmid:17030551
- 31. The DHS Program—The DHS Wealth Index (English) 470 [Internet]. [cited 2016 Jul 7]. http://www.dhsprogram.com/publications/publication-cr6-comparative-reports.cfm
- 32. Mundy KM, Nichols E, Lindsey J. Socioeconomic Disparities in Cataract Prevalence, Characteristics, and Management. Seminars in Ophthalmology. 2016 Jul 3;31(4):358–63. pmid:27100947
- 33. Kuper H, Polack S, Eusebio C, Mathenge W, Wadud Z, Foster A. A Case-Control Study to Assess the Relationship between Poverty and Visual Impairment from Cataract in Kenya, the Philippines, and Bangladesh. PLOS Medicine. 2008 Dec 16;5(12):e244. pmid:19090614
- 34. Abdou A, Nassirou B, Kadri B, Moussa F, Munoz BE, Opong E, et al. Prevalence and risk factors for trachoma and ocular Chlamydia trachomatis infection in Niger. Br J Ophthalmol. 2007 Jan;91(1):13–7. pmid:16899525
- 35. Seddon J, Fong D, West SK, Valmadrid CT. Epidemiology of risk factors for age-related cataract. Survey of Ophthalmology. 1995 Jan 1;39(4):323–34. pmid:7725232
- 36. Addissie A, Davey G, Newport MJ, Addissie T, MacGregor H, Feleke Y, et al. 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. pmid:24885049
- 37. Federal Democratic Republic of Ethiopia Ministry of Health: Second Edition of National Neglected Tropical Diseases Master Plan, Addis Ababa 2016.
- 38. Taye B, Alemayehu B, Birhanu A, Desta K, Addisu S, Petros B, et al. Podoconiosis and Soil-Transmitted Helminths (STHs): Double Burden of Neglected Tropical Diseases in Wolaita Zone, Rural Southern Ethiopia. PLOS Neglected Tropical Diseases. 2013 Mar 14.
- 39. The SAFE Strategy | International Trachoma Initiative [Internet]. [cited 2016 Jul 14]. http://trachoma.org/safe-strategy
- 40. WHO | Water sanitation and hygiene for accelerating and sustaining progress on neglected tropical diseases [Internet]. WHO. [cited 2016 Jul 14]. http://www.who.int/water_sanitation_health/publications/wash-and-ntd-strategy/en/
- 41. Samuel Tasew F. Podoconiosis, the Non-Filarial Elephantiasis, a Means of Discrimination and Poverty in Ethiopia. American Journal of Biomedical and Life Sciences. 2015;3(3):67.
- 42. Habtamu E, Wondie T, Aweke S, Tadesse Z, Zerihun M, Zewdie Z, et al. Trachoma and Relative Poverty: A Case-Control Study. PLOS Negl Trop Dis. 2015 Nov 23;9(11):e0004228. pmid:26600211
- 43. Tsegay G, Wubie M, Degu G, Tamiru A, Cooper M, Davey G. Barriers to access and re-attendance for treatment of podoconiosis: a qualitative study in northern Ethiopia. Int Health. 2015 Jul 1;7(4):285–92. pmid:25540135
- 44. Addisu S, El-Metwally T h., Davey G, Worku Y, Titheradge M a. The role of transforming growth factor-β1 and oxidative stress in podoconiosis pathogenesis. British Journal of Dermatology. 2010 May 1;162(5):998–1003. pmid:20199540
- 45. Burton MJ, Rajak SN, Hu VH, Ramadhani A, Habtamu E, Massae P, et al. Pathogenesis of Progressive Scarring Trachoma in Ethiopia and Tanzania and Its Implications for Disease Control: Two Cohort Studies. PLOS Negl Trop Dis. 2015 May 13;9(5):e0003763. pmid:25970613
- 46. Price EW, Henderson WJ. The elemental content of lymphatic tissues of barefooted people in Ethiopia, with reference to endemic elephantiasis of the lower legs. Trans R Soc Trop Med Hyg. 1978 Jan 1;72(2):132–6. pmid:653784
- 47. Blanke JH, Price EW, Rendell HM, Terry J, Townsend PD, Wintle AG, 1983. Correlations between elephantiasis and thermoluminescence of volcanic soils. Rad. Effects., 73, 103–113.
- 48. Molla YB, Wardrop NA, Le Blond JS, Baxter P, Newport MJ, Atkinson PM, et al. Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis. International Journal of Health Geographics. 2014;13:24. pmid:24946801
- 49. Price EW, McHardy WJ, Pooley FD. Endemic elephantiasis of the lower legs as a health hazard of barefooted agriculturalists in Cameroon, West Africa. Ann Occup Hyg. 1981; 24:1–8. pmid:7235457
- 50. Taylor HR, Siler JA, Mkocha HA, Munoz B, West S. The natural history of endemic trachoma: a longitudinal study. Am J Trop Med Hyg 1992;46(5):552–559. pmid:1599049
- 51. White A, Bogh J, Leheny W, Kuchipudi P, Varghese M, Riyami HA, et al. HLA antigens in Omanis with blinding trachoma: markers for disease susceptibility and resistance. Br J Ophthalmol. 1997 Jun;81(6):431–4. pmid:9274403
- 52. Mousley E, Deribe K, Tamiru A, Tomczyk S, Hanlon C, Davey G. Mental distress and podoconiosis in Northern Ethiopia: a comparative cross-sectional study. Int Health. 2015 Jan;7(1):16–25. pmid:25062906
- 53. Bartlett J, Deribe K, Tamiru A, Amberbir T, Medhin G, Malik M, et al. Depression and disability in people with podoconiosis: a comparative cross-sectional study in rural Northern Ethiopia. Int Health. 2016 Feb;8(2):124–31. pmid:26113669
- 54. Poverty and Blindness: A Survey of the Literature [Internet]. VISION 2020 UK. 2006 [cited 2016 Jul 1]. http://www.vision2020uk.org.uk/poverty-and-blindness-a-survey-of-the-literature/
- 55. Mousley E, Deribe K, Tamiru A, Davey G. The impact of podoconiosis on quality of life in Northern Ethiopia. Health and Quality of Life Outcomes. 2013;11:122. pmid:23866905
- 56. Habtamu E, Wondie T, Aweke S, Tadesse Z, Zerihun M, Mohammed A, et al. Impact of Trichiasis Surgery on Quality of Life: A Longitudinal Study in Ethiopia. PLoS Negl Trop Dis. 2016 Apr;10(4):e0004627. pmid:27078493