This study identified specific soil characteristics associated with increased prevalence of podoconiosis. Using environmental and individual data across an area with a wide spectrum of podoconiosis prevalence, the study filled the research gap from previous studies where the soil composition was not directly assessed in areas where study participants lived, or where soil composition was assessed in areas dichotomized into endemic or non-endemic, based on expert opinion and without prevalence data. In addition, recent developments in soil chemical analysis techniques and advances in geospatial and statistical methods enabled us to explore environmental data more extensively than was possible previously.
We found that the prevalence of podoconiosis was positively associated with the quantities of smectite, mica and quartz (crystalline silica) measured in the soil. The correlation between podoconiosis and smectite was larger than that between podoconiosis and other phyllosilicate minerals within the soil (kaolinite, chlorite and mica) or quartz. Smectite is classified as a 2:1 phyllosilicate, with a structure in which two tetrahedral silicate sheets sandwich a central octahedral silicate sheet. In general, 2:1 phyllosilicates have large surface areas, are able to undergo isomorphous substitution (ion exchange within its structure) and hence have elevated surface reactivity. The presence of 2:1 phyllosilicates in soils typically results in the deposits displaying distinctive characteristics such as high cation exchange capacity and shrink-swell properties. Smectite has unique properties of water absorption and expansion, and is able to modify water flow.
The biological properties of smectite have mostly been investigated in relation to gastrointestinal and dermatological therapeutic effects. Smectites are known as dermatological protectors because of their ability to adhere to the skin, form a protective film and absorb greases and toxins[13, 14]. However, these properties of adherence and water absorption might potentially, through establishment of an external water gradient influencing permeability of the stratum corneum, increase transdermal uptake of potential toxins. Release and transdermal uptake of a range of ions bound to pelotherapy clays has been demonstrated, 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 (O2−) and hydroxyl radicals (HO) in the early stages. 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.
Other studies have investigated the effects of clays on infection. Montmorillonite, a form of phyllosilicate within the smectite group that typically results from the weathering of volcanic ash, was noted in the 1970s to have a greater infection potentiation effect than other phyllosilicates (kaolinite and illite). The mechanism was later explained to be the direct cytotoxic effect of montmorillonite on neutrophils, weakening cell immunity and facilitating bacterial proliferation[18, 19]. A very recent study, in 2013, suggests that montmorillonite facilitates the survival of strains of enteropathogenic bacteria (microorganisms causing diseases of the intestine) in the soil by providing mineral nutrients and enabling respiratory simulation. On the other hand, other studies have demonstrated the bactericidal effects of hydrated clay in which cell death occurs by “exchange of soluble clay constituents toxic to the bacteria”[21, 22]. Williams et al. noted that expandable clay minerals, particularly illite-smectite, had the most pronounced antibacterial properties due to extreme pH and Fe concentration, and Otto and Haydel demonstrated that illite-smectite rich clay mixtures acquire powerful antibacterial activity due to their positive correlation with concentration of Cu2+ and Zn2+ ions, rather than their negative correlation with Fe3+ or lack of correlation with pH. These effects of clay mineral types in infection and our finding of strong associations between podoconiosis and soil smectite concentrations may help explain the pathogenesis of episodes of super-infection and acute adenolymphangitis (a frequent complication of podoconiosis characterized by hot, painful, and reddened swelling of the lymphedematous legs)[23–25].
Mica and quartz were also significantly associated with increased prevalence of podoconiosis. Previously, several researchers had independently observed the presence of clay minerals such as kaolinite and smectite in the soil samples they analysed[4, 5, 7, 8]. Price et al. found amorphous silica and aluminium oxides in the lymph nodes of podoconiosis cases and postulated that these minerals, particularly silica, may be involved in the pathogenesis of podoconiosis[4, 5]. Frommel et al. suggested that the high level of trace elements, such as Zr, within the soil found in podoconiosis-endemic areas was responsible for the development of podoconiosis[6–8]. Several studies lend biological plausibility to our finding of positive associations between quartz (a form of crystalline silica ubiquitous in the environment) and prevalence of podoconiosis: quartz (i) has been demonstrated to induce an inflammatory response and fibrosis in the pathogenesis of lung silicosis[26–28]; (ii) is listed as a Group 1 carcinogen by the International Agency for Research on Cancer; (iii) has been shown to be more toxic to the human body than amorphous silica; and (iv) animal models have shown lymphatic fibrosis and blockage comparable to that found in podoconiosis on injection of crystalline silica suspension into the lower limbs of rabbits.
Multiple studies indicate that zirconium is unlikely to have a pathologic role in the human body[31, 32]. Our univariate analysis finding of elevated zirconium in podoconiosis-endemic areas may suggest that this element plays another role, such as in facilitating dryness and cracking of skin on the feet. A recent study in Ethiopia showed that podoconiosis cases had lower stratum corneum hydration than unaffected controls, resulting in skin dryness and cracking which, in turn, may facilitate the ingress of mineral particles or microorganisms through the skin barrier. The ability of zirconium to accumulate in skin stratum corneum and sometimes to cause skin granuloma (inflammation) has been documented[33, 34]. Adding zirconium to commonly used aluminium chloride antiperspirants increases antiperspirant efficacy, and application of non-emollient antiperspirants was also shown to reduce sweat moisture in feet. Zirconium is a trace element in soil and so exists in very small amounts, thus our observation may simply reflect the association of zirconium with other soil elements. However, it is also possible that chronic exposure to zirconium in the soil plays a role in dehydration and cracking of the skin of the feet, thereby predisposing to podoconiosis.
Our model captured 40% of the variation in podoconiosis prevalence. The regression residuals indicate that the development of podoconiosis depends on etiological factors other than purely environmental factors. Genetic susceptibility has been shown to be another key aetiological factor, as have shoe-wearing practices[37, 38]. This study had limited capability to capture individual behaviours, disease severity and genetic variations in relation with environmental factors that are also likely to have been important factors in explaining the residual variation[39, 40]. However, the soil composition factors identified by our analyses will be valuable to enhance our understanding of the development of podoconiosis in areas where the majority of people walk barefoot.