The role of transforming growth factor-β1 and oxidative stress in podoconiosis pathogenesis

Addisu, Sisay; Davey, Gail; Worku, Yoseph; Titheradge, Michael A.

doi:10.1111/j.1365-2133.2010.09652.x

Cited by 16 publications

(13 citation statements)

References 42 publications

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“…The odd of Podoconiosis was 3.85 times higher in the male gender. This finding is different from other scholarly findings ( 32 , 33 ). This might be due to the different exposure distribution of predictors of Podoconiosis in these areas.…”

Section: Discussioncontrasting

confidence: 99%

Determinants of podoconiosis, a case control study

Feleke

2017

Ethiop J Health Sci

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Section: Discussioncontrasting

confidence: 99%

Determinants of podoconiosis, a case control study

Feleke

2017

Ethiop J Health Sci

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“…Release and transdermal uptake of a range of ions bound to pelotherapy clays has been demonstrated [16], so it is possible that ionic species adsorbed to clays of podoconiosis endemic areas are exchanged across the skin of the lower leg and foot. A study of the role of inflammatory biomarkers for development of podoconiosis has indicated increased anion (O 2 − ) and hydroxyl radicals (HO) in the early stages [17]. The major source of these peroxides was suggested to be activation and subsequent elimination of macrophages, which might relate to soil minerals with high oxidation properties.…”

Section: Discussionmentioning

confidence: 99%

Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

et al. 2014

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IntroductionThe 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.MethodsFieldwork 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.ResultsPodoconiosis 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.ConclusionsMore 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.

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“…Podoconiosis is thought to be the result of abnormal inflammatory responses to one or more mineral triggers. Little is known of the mediators involved in this inflammatory process, though transforming growth factor β may play a role [16]. We hypothesized that patients with podoconiosis might manifest an anemia of chronic disease, and that anemia might be more pronounced in the presence of anemia-causing intestinal helminths.…”

Section: Introductionmentioning

confidence: 99%

Podoconiosis and Soil-Transmitted Helminths (STHs): Double Burden of Neglected Tropical Diseases in Wolaita Zone, Rural Southern Ethiopia

et al. 2013

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BackgroundBoth podoconiosis and soil-transmitted helminth (STH) infections occur among barefoot people in areas of extreme poverty; however, their co-morbidity has not previously been investigated. We explored the overlap of STH infection and podoconiosis in Southern Ethiopia and quantified their separate and combined effects on prevalent anemia and hemoglobin levels in podoconiosis patients and health controls from the same area.Methods and Principal FindingsA two-part comparative cross-sectional study was conducted in Wolaita zone, southern Ethiopia. Data were collected from adult patients presenting with clinically confirmed podoconiosis, and unmatched adult neighborhood controls living in the same administrative area. Information on demographic and selected lifestyle factors was collected using interviewer-administered questionnaires. Stool samples were collected and examined qualitatively using the modified formalin-ether sedimentation method. Hemoglobin level was determined using two different methods: hemoglobinometer and automated hematology analyzer. A total of 913 study subjects (677 podoconiosis patients and 236 controls) participated. The prevalence of any STH infection was 47.6% among patients and 33.1% among controls (p<0.001). The prevalence of both hookworm and Trichuris trichiura infections was significantly higher in podoconiosis patients than in controls (AOR 1.74, 95% CI 1.25 to2.42, AOR 6.53, 95% CI 2.34 to 18.22, respectively). Not wearing shoes and being a farmer remained significant independent predictors of infection with any STH. There was a significant interaction between STH infection and podoconiosis on reduction of hemoglobin level (interaction p value = 0.002).ConclusionsPrevalence of any STH and hookworm infection was higher among podoconiosis patients than among controls. A significant reduction in hemoglobin level was observed among podoconiosis patients co-infected with hookworm and ‘non-hookworm STH’. Promotion of consistent shoe-wearing practices may have double advantages in controlling both podoconiosis and hookworm infection in the study area.

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The role of transforming growth factor-β1 and oxidative stress in podoconiosis pathogenesis

Abstract: This is the first study, to our knowledge, to attempt to elucidate the molecular pathogenetic events in podoconiosis. We conclude that TGF-beta1 may have a pathogenetic role, with oxidative stress playing a minor role in the early stages of disease.

Cited by 16 publications

References 42 publications

Determinants of podoconiosis, a case control study

Determinants of podoconiosis, a case control study

Modelling environmental factors correlated with podoconiosis: a geospatial study of non-filarial elephantiasis

Podoconiosis and Soil-Transmitted Helminths (STHs): Double Burden of Neglected Tropical Diseases in Wolaita Zone, Rural Southern Ethiopia

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