10.5 Podoconiosis (nonfilarial elephantiasis) 1833

10.5 Podoconiosis (nonfilarial elephantiasis) 1833

10.5 Podoconiosis (non​filarial elephantiasis) Gail Davey ESSENTIALS Podoconiosis is the lesser-​known of the two major forms of trop- ical lymphoedema. The disease affects genetically susceptible indi- viduals who go barefoot and whose feet and legs are exposed long term to red clay soils. It is found focally across tropical Africa, Central America, and North India where such soils coexist with high altitude, high rainfall, and low-​income populations. Prodromal symptoms include itching and a burning sensation in the foot; early changes include spreading or ‘splaying’ of the forefoot and leakage of col- ourless ‘lymph’ fluid’. Later stages are manifested by lymphoedema, which is usually bilateral and limited to below the knee. Early stage disease is reversible through good foot hygiene and use of socks and shoes. Late-​stage disease, which results in considerable economic and social difficulties, is treated with foot hygiene, bandaging, socks and shoes, elevation, and (if necessary) nodulectomy. The disease’s later stages result in considerable economic and social hardship and, despite treatment, may never fully resolve. Aetiology and pathogenesis Spatial analysis has been used to link environmental factors with occurrence of podoconiosis. These include altitude (between 1000 and 2500 metres above sea level), annual precipitation (>1250  mm), higher vegetation index, and population density. Similar approaches have been used on a smaller scale to investi- gate associations between specific mineral constituents of soil and disease, with phyllosilicate materials (smectite clays and mica), quartz, iron oxide, and zirconium associated with podoconiosis prevalence. Not everyone exposed to these soils develops podoconiosis, but family clustering has long been observed. Recent genetic studies demonstrated high heritability of the trait and segregation analysis suggests the presence of an autosomal codominant major gene con- ferring susceptibility to podoconiosis. A genome-​wide association study demonstrated association between variants in HLA class II loci and podoconiosis, suggesting that the disease may be a T-​cell-​ mediated inflammatory disease. The best evidence to date suggests that podoconiosis is the re- sult of an abnormal inflammatory reaction to mineral particles that penetrate the skin and accumulate in the lower leg. Colloid-​sized particles of elements common in irritant clays (aluminium, silicon, magnesium, and iron) have been demonstrated in the lower limb lymph node macrophages of both patients and non​patients living barefoot on the clays. Electron microscopy of lymph nodes shows evidence of follicular hyperplasia, with an increased number of pro- liferative germinal centres. An exaggerated lymphocyte population (predominantly CD4+ T lymphocytes) is seen in the paracortex sinuses of some of the nodes. Epidemiology Podoconiosis has been reported from highland areas of tropical Africa, Central America, and north-​west India (Fig. 10.5.1). Africa appears to be the most endemic World Health Organization (WHO) region:  high prevalence areas have been confirmed in Ethiopia, Cameroon, Rwanda, Uganda and Kenya, and were previously re- ported in Tanzania, Equatorial Guinea, the islands of Bioko, São Tomé, and Principe, and Cabo Verde. Recent nationwide mapping of podoconiosis in Ethiopia, the most heavily endemic country in the world, suggests that 1.54 million individuals, or 4% of the adult population, live with podoconiosis, and almost half the population (47.8%) live in areas environmentally suitable for the development of podoconiosis. The condition has been reported in the Central American highlands from Mexico, south to Ecuador, but recent work suggests very few new cases in these areas. Podoconiosis has also been reported in north-​west India, Sri Lanka, and Indonesia. Large-​scale population studies in Ethiopia indicate that being fe- male, older, unmarried, washing the feet less frequently than daily, and being semi-​skilled or unemployed are all associated with in- creased risk of podoconiosis. All major community-​based studies have shown onset in the first or second decade and a progressive increase in prevalence up to the sixth decade.

SECTION 10  Environmental medicine, occupational medicine, and poisoning 1834 Clinical, economic, and social burdens Studies have documented that 77.4% to 97% of patients have experi- enced ‘acute attacks’ (acute dermatolymphangioadenitis or ADLA) at least once per year. These are episodes of inflammatory swelling of lymphoedematous legs that may be triggered by bacterial, viral, or fungal superinfection. They are characterized by hot, painful, and reddened swelling and lead to loss of productivity. According to a study in southern Ethiopia in an area with 1.7 mil- lion residents, the annual economic cost of podoconiosis was more than 16 million USD per year, which when extrapolated to the country as a whole, suggests cost of more than 200 million USD per annum for Ethiopia. People with podoconiosis were found to be half as pro- ductive as those without podoconiosis but with the same occupations. The social impact of podoconiosis is also significant. Qualitative studies in southern Ethiopia have shown that widespread miscon- ceptions about the causes, prevention, and treatment of podoconiosis have contributed to it being considered the most stigmatizing health problem in endemic areas. This is manifested in patients being ex- cluded from school, denied participation in local meetings, churches and mosques, and excluded from marrying unaffected individuals. Affected individuals report lower quality of life, higher levels of mental distress, and higher levels of depression than their healthy neighbours. Clinical features The disease process is usually described in three phases: prodromal, early, and advanced. Prodromal symptoms include itching of the skin of the forefoot, a burning sensation in the foot and lower leg, ‘chills’, or generalized joint pains. The affected person may describe exacerbation of symptoms when they try to walk long distances or do hard physical work. Early changes include spreading or ‘splaying’ of the forefoot, swelling of the sole of the foot, leakage of colourless ‘lymph’ fluid from the foot, and changes in the skin so that it looks like moss or velvet (Fig. 10.5.2). The affected person may report limb aches, heaviness of the lower leg and foot, and odour from the lymph leak, which may attract flies. As the lymphoedema progresses, both legs and feet will be af- fected, though one is usually more severely affected than the other. Fig. 10.5.2  Early changes—​oedema, block toes, changes in skin colour (here related to the pattern of the open sandal worn), lymph ooze, and early mossy changes around interdigital clefts. 0.21–0.30 0.31–0.99 1.00–2.51 2.52–4.62 Average Prevalence (%) based on available data Case report Not reporting Reported Presence Fig. 10.5.1  Geographical distribution of prevalence of podoconiosis—dots represent island nations. Source data from Deribe K, et al. (2015). The feasibility of elimination of podoconiosis. Bull WHO, 93, 712–18.

10.5  Podoconiosis (nonfilarial elephantiasis) 1835 In advanced disease, the swelling may be soft and fluid swelling (‘water-​bag’ type, Fig. 10.5.3), hard and fibrotic swelling (‘leathery’ type, Fig. 10.5.4), or a mix of these two. Differential diagnosis Podoconiosis must be distinguished from lymphoedema caused by filariasis (see Table 10.5.1), leprosy, onchocerciasis, rheumatic heart disease, pelvic surgery, and Milroy’s disease. Clinical investigation In the community, diagnosis is usually based on the features given in Table 10.5.1. A  more comprehensive algorithm that excludes lymphatic filariasis through antigen and antibody testing has been developed for mapping studies. Each foot should be assessed for mossy changes, interdigital maceration, wounds, and stage of dis- ease according to the five-​level Tekola staging system. Prevention Evidence suggests that primary prevention should consist of avoiding prolonged contact between the skin and irritant soils through the regular wearing of closed shoes. Daily foot hygiene is also important for prevention, as is covering mud floors of traditional houses. ‘Community conversations’ have been suc- cessfully used in endemic areas to provide information about the causes of podoconiosis and to encourage preventive behavioural changes. Treatment Treatment of podoconiosis lymphoedema is aimed at reducing the frequency of acute attacks, restoration of the barrier function of the skin, and reduction of exposure to irritant soil. A simple package of self-​care measures including foot hygiene, ointment, Fig. 10.5.3  ‘Water-​bag’ type swelling: patient in her early 20s. Fig. 10.5.4  ‘Leathery’ type advanced podoconiosis in patient aged 14. Table 10.5.1  Distinguishing podoconiosis from lymphatic filariasis Characteristic LF Podoconiosis Area of residence <1000 m above sea level

1500 m above sea level Chief cause Mosquito-​borne parasite Genetic susceptibility plus long-​term exposure to irritant highland soil Diagnosis Field ‘ICT’ blood test Exclusion of other cause of leg swelling Site of first symptom Any part of limb except foot Toes and foot Lymph node ‘attacks’ Precede swelling of limb Follow swelling of limb Chief site of swelling Above and below knee Below knee Prevention Mosquito nets Mass Drug Administration (MDA) Protective footwear Floor coverings Foot washing Treatment 2 drugs (albendazole + DEC) Foot hygiene Foot hygiene, bandages, exercises, socks and shoes

SECTION 10  Environmental medicine, occupational medicine, and poisoning 1836 bandages, elevation, exercises, and use of socks and shoes has re- cently been shown to reduce the incidence and duration of acute attacks. Charles’s operation (removal of skin, subcutaneous tissue, and deep fascia to lay the muscles and tendons bare, followed by grafting of healthy skin), is no longer recommended, as long-​term results are disappointing. Nodulectomy may be required if one or two nodules prevent use of footwear, and follow-​up has shown skin healing postnodulectomy to be good. Prognosis Recent follow-​up during a community-​based trial suggests excess mortality associated with podoconiosis. Untreated patients have severely reduced mobility and work capacity by their mid-​40s, chiefly due to episodes of acute dermatolymphangioadenitis. Global awareness Podoconiosis was included in the WHO list of ‘Other Neglected Tropical Conditions’ in February 2011, and is currently addressed under the lymphatic filariasis programme of the Department for Control of Neglected Tropical Diseases (NTDs). Elimination of podoconiosis as a public health problem is achievable be- cause no biological agent or vector involved in podoconiosis has been identified, the global scale of the problem is relatively small, and the strategies for podoconiosis prevention and control are safe. A national network, the National Podoconiosis Action Network, and a global initiative, Footwork, the International Podoconiosis Initiative (https://​podo.org), were launched in 2012. These aim to advocate for and coordinate integration of podoconiosis inter- ventions into NTD control strategies at national and international levels. Together with non​government partners, Footwork has coord- inated training of health workers in podoconiosis management in Cameroon and Uganda and will provide similar training in Rwanda and Burundi. Likely research developments The Global Atlas of Podoconiosis project was launched in 2017 to further understanding of the geographical distribution and spatial epidemiology of the disease. Studies examining host im- munological and inflammatory responses are currently underway. A range of devices to enable better diagnosis and volume meas- urement are being developed and tested, while a trial examining the effectiveness of doxycycline has recently been launched in Cameroon. Implementation research exploring optimal integration of podoconiosis care into existing health systems is also underway. FURTHER READING Deribe K, Cano J, Trueba ML, Newport MJ, Davey G. (2018). Global epidemiology of podoconiosis: a systematic review. PLoS Negl Trop Dis, 12(3), e0006324. Deribe K, et al. (2015). The feasibility of elimination of podoconiosis. Bull WHO, 93, 712–​18. Negussie H, et al. (2018). Lymphoedema management to prevent acute dermatolymphangioadenitis in podoconiosis in northern Ethiopia (GoLBet): a pragmatic randomised controlled trial. The Lancet Global Health, 6(7), e795–​e803. Tekola F, et  al. (2006). Economic costs of podoconiosis (endemic non-​filarial elephantiasis) in Wolaita Zone, Ethiopia. Trop Med Int Health, 11, 1136–​44. Tekola F, et al. (2012). The HLA class II locus confers susceptibility to podoconiosis. N Engl J Med, 388, 1200–​8.

SECTION 11 Nutrition Section editor: Katherine Younger 11.1 Nutrition: Macronutrient metabolism  1839 Keith N. Frayn and Rhys D. Evans 11.2 Vitamins  1855 Tom R. Hill and David A. Bender 11.3 Minerals and trace elements  1871 Katherine Younger 11.4 Severe malnutrition  1880 Alan A. Jackson 11.5 Diseases of affluent societies and the need
for dietary change  1891 J.I. Mann and A.S. Truswell 11.6 Obesity  1903 I. Sadaf Farooqi 11.7 Artificial nutrition support  1914 Jeremy Woodward