The feasibility of eliminating podoconiosis
Kebede Deribe a, Samuel Wanji b, Oumer Shafi c, Edrida M Tukahebwa d, Irenee Umulisa e, David H Molyneux f & Gail Davey a
a. Brighton and Sussex Medical School, Falmer Campus, Brighton, BN1 9PX, England.
b. Department of Biochemistry and Microbiology, University of Buea, Buea, Cameroon.
c. Federal Ministry of Health, Addis Ababa, Ethiopia.
d. Vector Control Division, Ministry of Health, Kampala, Uganda.
e. Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Center, Kigali, Rwanda.
f. Lymphatic Filariasis Support Centre, Liverpool School of Tropical Medicine, Liverpool, England.
Correspondence to Kebede Deribe (email: email@example.com).
(Submitted: 11 November 2014 – Revised version received: 15 May 2015 – Accepted: 10 June 2015 – Published online: 21 August 2015.)
Bulletin of the World Health Organization 2015;93:712-718. doi: http://dx.doi.org/10.2471/BLT.14.150276
In 2012, the World Health Organization (WHO) published targets for the elimination of neglected tropical diseases or reductions in their impact to levels at which they are no longer considered public-health problems (Table 1).1, 2 Elimination is an attractive, motivating and powerful concept that attracts bold thinkers, increases political commitment, mobilizes donors and resources, encourages innovations and motivates health workers.4 It also encourages service expansion and provides access to hard-to-reach communities. Some researchers and policy-makers argue that elimination programmes may not be cost effective, may divert resources from other priorities and weaken or even destroy other disease control programmes.5–7 However, elimination is an attractive investment because – if the elimination effort is successful – any time-limited surge in spending should lead to long-term savings.8 Some definitions of important terms used by WHO in this context are listed in Box 1.
Table 1. Neglected tropical diseases and targets for their elimination set by the World Health Organization
Box 1. World Health Organization’s definition of terms used in elimination and eradication efforts9,10
Reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a result of deliberate efforts – with continued intervention measures required to maintain the reduction.
Elimination of disease
Reduction to zero of the incidence of a specified disease in a defined geographical area as a result of deliberate efforts – with continued intervention measures required to maintain the elimination.
Elimination of infection
Reduction to zero of the incidence of infection caused by a specified agent in a defined geographical area as a result of deliberate efforts – with continued measures required to prevent the re-establishment of transmission.
Elimination as a public-health problem
Control of the manifestations of a disease – at an arbitrarily defined qualitative or quantitative level – so that the disease is no longer considered a public-health problem.
Permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts – with intervention measures no longer needed.
Complete removal of the specific infectious agent so that it no longer exists in nature or the laboratory.
Podoconiosis (non-filarial elephantiasis) – an inflammatory disease caused by prolonged contact with irritant minerals in soil – was identified by WHO as a neglected tropical disease in 2011, but no global target has been set for its elimination.11 In recent years, there has been remarkable progress on podoconiosis research; the commitment of endemic countries to podoconiosis control has increased and elimination is now on the global health agenda.11 In this paper, we describe the symptoms of the disease, its socioeconomic impact, strategies for control and the feasibility of elimination.
Symptoms and diagnosis
At present, podoconiosis can only be diagnosed clinically from characteristic signs of the disease and the exclusion of infectious and hereditary causes of lymphoedema.12 The key early signs of podoconiosis are splaying of the forefoot, swelling of the foot and lower leg that disappears after overnight rest, thickening of the skin over the dorsum of the foot, and moss-like rough, warty growths on the feet.13–15 With time, the swelling of affected legs (lymphoedema) becomes either soft and pitting or nodular and fibrotic. Late-stage disease is characterized by fusion of the toes and joint stiffness.13–16 The patient’s history and the results of a physical examination and certain disease-specific tests may allow filarial elephantiasis, lymphoedema of systemic disease or leprosy to be excluded.17
Although there are point-of-care diagnostic tests for lymphatic filariasis, such tests are not very sensitive in detecting filarial infection among advanced cases. The absence of any point-of-care tests for the diagnosis of podoconiosis is a continued challenge, especially when considering the disease’s elimination. Until such diagnostic tests are designed, the standardization of the disease’s clinical diagnosis will remain important and will involve establishing the predictive value of each of the various signs and symptoms. Previous studies have indicated that clinical diagnosis is an accurate and workable approach in settings where podoconiosis is endemic.18 Similar studies now need to be conducted in settings in which lymphatic filariasis and podoconiosis may overlap. The effectiveness of clinical diagnosis in excluding other causes of lymphoedema needs to be formally evaluated.
Podoconiosis has severe health, social and economic consequences.19 According to a study in Ethiopia, the annual economic cost of podoconiosis in an area with 1.7 million residents was more than 16 million United States dollars (US$).19 When extrapolated to the national population, this result indicates a corresponding cost of more than US$ 200 million. People with podoconiosis were found to lose 45% of their economically productive time because of morbidity associated with the disease.19 Most people with podoconiosis in Ethiopia experience an episode of acute inflammation that may be triggered by bacterial, viral or fungal infection, at least once per year.20–22 Such acute attacks are characterized by hot, painful and reddened swelling. Since podoconiosis patients become bedridden during such attacks, it leads to loss of productivity.
The social impact of podoconiosis is also substantial. In endemic areas of southern Ethiopia, the disease is considered to be the most stigmatizing health problem23,24 and affected people may be excluded from school, denied participation in local meetings, churches and mosques and excluded from marriage with unaffected individuals.23–27 In the same areas, most community members investigated were found to have negative, stigmatizing attitudes towards social interactions with people affected by podoconiosis.25 In northern Ethiopia, people with podoconiosis were found to have much lower quality-of-life scores, in all domains of quality of life, than healthy people from the same neighbourhoods.28
The burden of podoconiosis will be estimated for the first time in the 2015 round of the Global burden of disease study.29 Clearly-generated disability-weight measurements and the inclusion in any assessment of the multiple impacts of podoconiosis – including acute attacks – should enable reasonably accurate estimates of the numbers of disability-adjusted life years lost because of the disease.
Strategies aimed at addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence.13 Although the disease was probably once common in Algeria, the Canary Islands, Morocco and Tunisia, it has disappeared from these areas as the result of urbanization and socioeconomic development and the consequent, almost universal, use of shoes.13 Specific strategies for podoconiosis control may be divided into primary, secondary and tertiary prevention.30 Primary prevention – i.e. the prevention of contact between feet and the minerals in the irritant soil that trigger the inflammatory process – includes the use of shoes, 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 attacks.
The objectives of secondary and tertiary prevention are to arrest progress of early disease, reduce the frequency of acute attacks and reduce the swelling of the limbs. Surgical removal of nodules may be indicated.31 Management of lymphoedema can lead to modest clinical improvement and substantial improvements in quality of life.32 The effectiveness and cost–effectiveness of these interventions are being evaluated.33
Much of the available information on podoconiosis treatment and prevention comes from Ethiopia.30,34 Local strategies include the distribution of shoes in schools35 and integration with the national community-based health extension programme. In a small study in northern Ethiopia, over a third of people were willing to pay at least half of the cost of care and over 30% were willing to pay the full cost of shoes.36
Use of shoes also has benefits in the fight against several other neglected tropical diseases.37 There is likely to be synergy between the elimination of podoconiosis and the elimination of lymphatic filariasis. The latter has two pillars: (i) transmission interruption via mass drug administrations and (ii) clinical care and disability prevention.38 It should be relatively easy to use the second pillar for both diseases.
Societal and political considerations
There is a growing political commitment for interventions against podoconiosis. In the absence of any relevant global strategies, several endemic countries have taken independent initiatives to address the challenges of control. For example, the Ethiopian Government identified podoconiosis as one of its eight priority neglected tropical diseases and included the disease in its 2013–2015 integrated master plan for the control of such diseases.39 Ethiopia and Rwanda, (personal communication available from author), have each mapped the geographical distribution of podoconiosis nationwide.12,17 The only potentially endemic country that is currently experiencing severe political unrest is the Democratic Republic of the Congo, where the burden of podoconiosis – and the feasibility of its elimination – have yet to be studied. Risk maps can be developed based on the available evidence of environmental factors that are predictive of podoconiosis.40
Since WHO included podoconiosis in its list of neglected tropical diseases, the international community has responded. The Wellcome Trust and the United States National Institutes of Health continue to be strong funders of podoconiosis research.41 The Big Lottery Fund (Manchester, United Kingdom) supports podoconiosis interventions financially42 and the TOMS® shoe company (Playa Del Rey, USA) is also an important funder of podoconiosis prevention and care – both through donations of children’s shoes and via direct financial support.42
Feasibility of elimination
The elimination of podoconiosis is likely to be feasible. The fact that the disease is not infectious makes elimination easier. As discussed above, use of shoes is a practical intervention for prevention of podoconiosis. Consistent use of shoes, regular foot hygiene and covering floors are the key preventive strategies against podoconiosis. Although these measures appear simple, there are social, practical and logistical challenges that hinder their acceptance by people living in endemic areas. Financial constraints, lack of appropriate shoes for wet and dry seasons and sociocultural factors all affect the availability and use of shoes. If shoes are to be used as a health intervention, innovative approaches are needed to make them affordable. Shoes also need to be appropriate to local activities and seasonal patterns.22,43
We have developed case definitions (Box 2) and elimination targets (Box 3) as a starting point for future efforts towards the elimination of podoconiosis. A global strategy for the elimination of this disabling disease is now needed, based on the evidence for both diagnosis and care. A clearer case for investment must be provided for funding agencies and endemic-country governments. The interventions for podoconiosis prevention and treatment are relatively simple. Restored function and improved quality of life can be achieved for people with lymphoedema after just three months of treatment.30,32 Promotion of shoes for podoconiosis prevention is likely to have multiple health benefits.37
Box 2. Case definitions of podoconiosis
Any lymphoedema of the lower limb of any duration.
Any lymphoedema of the lower limb present for more than one year in a resident of an endemic area.
Lymphoedema of the lower limb present for more than one year in a resident of an endemic area, for which other causes – e.g. onchocerciasis, lymphatic filariasis, leprosy, Milroy syndrome, heart failure and liver failure – have been excluded.
Box 3. Podoconiosis elimination targets
Elimination from an endemic district or implementation unit
Podoconiosis is considered to be eliminated if the prevalence of untreated podoconiosis among individuals aged ≥ 15 years is < 1%, and > 95% of lymphoedema cases are treated adequately after 10 years of programme implementation.
Elimination from country
Podoconiosis is considered to be eliminated when:
- prevalence of untreated podoconiosis among individuals aged ≥ 15 years, in every village sampled over a 10-year period, is < 1%;
- after 10 years of control programme implementation, the prevalence of early signs of podoconiosis among children aged 10–15 years is < 0.001%;
- protective shoes are worn by > 95% of the population in endemic districts; and
- almost all (> 95%) of the lymphoedema cases are treated adequately.
By integrating podoconiosis care into the wider context of general foot care – including for leprosy and lymphatic filariasis – it should be possible to avoid duplication of efforts and enable the available resources to be used efficiently.38 The continued challenge in providing clinical services at scale is a shortage of skilled health workers. In those countries where podoconiosis is endemic, most health workers lack the knowledge and practical skills needed to address the symptoms of lymphoedema.44 Clinical management needs to be included in these countries’ curricula for the pre- and in-service training of health-care providers. National accreditation bodies for health-care providers need to be engaged in efforts to eliminate podoconiosis, and the disease needs to be included in any continued professional development for health workers.
Access to treatment services for those in need is an important aspect of podoconiosis elimination. Clinical services are currently provided by just a few faith-based and nongovernmental organizations.30,32 Provision of free-of-charge or low-cost prevention and treatment, through government-led programmes, will probably be critical to any elimination effort.
We need advocacy for shoes as a health intervention. For those individuals who cannot afford to buy shoes, subsidized distribution – perhaps via collaboration with shoe companies – should be considered. The TOMS® shoe company currently provides a pair of shoes to a child at risk of podoconiosis for each pair of shoes it sells elsewhere.45 Extending similar collaborations to other shoe companies would be beneficial.
Finally, continued research should focus on the development of good point-of-care diagnostic tests for podoconiosis, which are needed both to detect new cases and, ultimately, to verify elimination. Although definitive diagnosis may not be a priority as elimination programmes are launched, robust, sensitive and specific diagnostic tests will certainly be needed as podoconiosis becomes rare.
KD and GD are supported by a Wellcome Trust PHATIC Training Fellowship (099876) and a Wellcome Trust University Award (091956), respectively.
- Country leadership and collaboration on neglected tropical diseases. Third progress report of the London Declaration. United to Combat Neglected Tropical Diseases; 2015. Available from: http://unitingtocombatntds.org/sites/default/files/document/UTCNTD%20FULL%20REPORT.pdf [cited 2015 Jul 1].
- Accelerating work to overcome the global impact of neglected tropical diseases. A roadmap for implementation. Geneva: World Health Organization; 2012. Available from: http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf [cited 2015 Jul 1].
- WHO meeting on elimination of human African trypanosomiasis (Trypanosoma brucei gambiense), 3–5 December 2012, Geneva. Geneva: World Health Organization; 2012. Available from: http://www.who.int/trypanosomiasis_african/hat_elimination_meeting_december_2012/en/ [cited 2015 Jul 1].
- Lockwood DN, Shetty V, Penna GO. Hazards of setting targets to eliminate disease: lessons from the leprosy elimination campaign. BMJ. 2014;348 feb07 5:g1136. http://dx.doi.org/10.1136/bmj.g1136 pmid: 24508610
- Barrett S. Economic considerations for the eradication endgame. Philos Trans R Soc Lond B Biol Sci. 2013 Aug 5;368(1623):20120149. http://dx.doi.org/10.1098/rstb.2012.0149 pmid: 23798697
- Fine PE. Leprosy: what is being “eliminated”? Bull World Health Organ. 2007 Jan;85(1):2. http://dx.doi.org/10.2471/BLT.06.039206 pmid: 17242748
- Kahn JG, Basu S, Boyle C, Hsiang MS, Jamison DT, Smith-Gueye C, et al. Financing elimination. In: Feachem RGA, Phillips AA, Targett GAT, editors. Shrinking the malaria map: a prospectus on malaria elimination. San Francisco: University of California; 2009. pp. 61–80.
- Whitty CJM. Milroy Lecture: eradication of disease: hype, hope and reality. Clin Med. 2014 Aug;14(4):419–21. http://dx.doi.org/10.7861/clinmedicine.14-4-419 pmid: 25099846
- Dayrit MM. Report of the workgroup on noninfectious diseases. Bull World Health Organ. 1998;76 Suppl 2:80–4, discussion 104–8. pmid: 10063680
- Dowdle WR. The principles of disease elimination and eradication. Bull World Health Organ. 1998;76 Suppl 2:22–5. pmid: 10063669
- Davey G, Bockarie M, Wanji S, Addiss D, Fuller C, Fox L, et al. Launch of the international podoconiosis initiative. Lancet. 2012 Mar 17;379(9820):1004. http://dx.doi.org/10.1016/S0140-6736(12)60427-9 pmid: 22423883
- 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;92(1):148–58. http://dx.doi.org/10.4269/ajtmh.14-0446 pmid: 25404069
- Price E. Podoconiosis: non-filarial elephantiasis. Oxford: Oxford Medical Publications; 1990.
- Price EW. Pre-elephantiasic stage of endemic nonfilarial elephantiasis of lower legs: “podoconiosis”. Trop Doct. 1984 Jul;14(3):115–9. pmid: 6464174
- Price EW. Endemic elephantiasis: early signs and symptoms, and control. Ethiop Med J. 1983 Oct;21(4):243–53. pmid: 6628370
- Cohen LB. Idiopathic lymphoedema of Ethiopia and Kenya. East Afr Med J. 1960 Feb;37:53–74. pmid: 13694397
- Sime H, Deribe K, Assefa A, Newport MJ, Enquselassie F, Gebretsadik A, et al. Integrated mapping of lymphatic filariasis and podoconiosis: lessons learnt from Ethiopia. Parasit Vectors. 2014;7(1):397. http://dx.doi.org/10.1186/1756-3305-7-397 pmid: 25164687
- Desta K, Ashine M, Davey G. Predictive value of clinical assessment of patients with podoconiosis in an endemic community setting. Trans R Soc Trop Med Hyg. 2007 Jun;101(6):621–3. http://dx.doi.org/10.1016/j.trstmh.2006.12.002 pmid: 17316723
- Tekola F, Mariam DH, Davey G. Economic costs of endemic non-filarial elephantiasis in Wolaita Zone, Ethiopia. Trop Med Int Health. 2006 Jul;11(7):1136–44. http://dx.doi.org/10.1111/j.1365-3156.2006.01658.x pmid: 16827714
- Tekola Ayele F, Alemu G, Davey G, Ahrens C. Community-based survey of podoconiosis in Bedele Zuria woreda, west Ethiopia. Int Health. 2013 Jun;5(2):119–25. http://dx.doi.org/10.1093/inthealth/iht003 pmid: 24030111
- Alemu G, Tekola Ayele F, Daniel T, Ahrens C, Davey G. Burden of podoconiosis in poor rural communities in Gulliso woreda, West Ethiopia. PLoS Negl Trop Dis. 2011 Jun;5(6):e1184. http://dx.doi.org/10.1371/journal.pntd.0001184 pmid: 21666795
- 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.
- Gebrehanna E. The social burden of podoconiosis in Wolaita zone. Addis Ababa: Addis Ababa University; 2005.
- 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. http://dx.doi.org/10.1016/j.inhe.2011.06.006 pmid: 24038367
- Yakob B, Deribe K, Davey G. High levels of misconceptions and stigma in a community highly endemic for podoconiosis in southern Ethiopia. Trans R Soc Trop Med Hyg. 2008 May;102(5):439–44. http://dx.doi.org/10.1016/j.trstmh.2008.01.023 pmid: 18339411
- Molla YB, Tomczyk S, Amberbir T, Tamiru A, Davey G. Patients’ perceptions of podoconiosis causes, prevention and consequences in East and West Gojam, Northern Ethiopia. BMC Public Health. 2012;12(1):828. http://dx.doi.org/10.1186/1471-2458-12-828 pmid: 23020758
- Tekola F, Bull S, Farsides B, Newport MJ, Adeyemo A, Rotimi CN, et al. Impact of social stigma on the process of obtaining informed consent for genetic research on podoconiosis: a qualitative study. BMC Med Ethics. 2009;10(1):13. http://dx.doi.org/10.1186/1472-6939-10-13 pmid: 19698115
- Mousley E, Deribe K, Tamiru A, Davey G. The impact of podoconiosis on quality of life in Northern Ethiopia. Health Qual Life Outcomes. 2013;11(1):122. http://dx.doi.org/10.1186/1477-7525-11-122 pmid: 23866905
- GBD 2015 Cause List. Seattle: Institute of Health Metrics and Evaluation; 2015. Available from: http://www.healthdata.org/sites/default/files/files/Projects/GBD/GBDcause_list.pdf [cited 2015 August 19].
- Davey G, Burridge E. Community-based control of a neglected tropical disease: the mossy foot treatment and prevention association. PLoS Negl Trop Dis. 2009;3(5):e424. http://dx.doi.org/10.1371/journal.pntd.0000424 pmid: 19479039
- Price EW. The management of endemic (non-filarial) elecphantiasis of the lower legs. Trop Doct. 1975 Apr;5(2):70–5. pmid: 1129853
- 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. http://dx.doi.org/10.1371/journal.pntd.0000902 pmid: 21152059
- Lang T, Clarke M, Newport M, Enquoselassie F, Loggerenberg F, Franzen S, et al. A research methodology study to map the process of initiating and operating a randomised controlled trial of podoconiosis treatment in northern Ethiopia. Trials. 2013;14(1) Suppl 1:O31. http://dx.doi.org/10.1186/1745-6215-14-S1-O31
- Tomczyk S, Tamiru A, Davey G. Addressing the neglected tropical disease podoconiosis in northern Ethiopia: lessons learned from a new community podoconiosis program. PLoS Negl Trop Dis. 2012;6(3):e1560.
- Tekola Ayele F, Adeyemo A, Rotimi CN. Using a “genomics tool” to develop disease prevention strategy in a low-income setting: lessons from the podoconiosis research project. J Community Genet. 2012 Oct;3(4):303–9. http://dx.doi.org/10.1007/s12687-012-0086-0 pmid: 22430163
- Tamiru A, Tsegay G, Wubie M, Gedefaw M, Tomczyk S, Tekola-Ayele F. Podoconiosis patients’ willingness to pay for treatment services in Northwest Ethiopia: potential for cost recovery. BMC Public Health. 2014;14(1):259. http://dx.doi.org/10.1186/1471-2458-14-259 pmid: 24642085
- Tomczyk S, Deribe K, Brooker SJ, Clark H, Rafique K, Knopp S, et al. Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2014 Nov;8(11):e3285. http://dx.doi.org/10.1371/journal.pntd.0003285 pmid: 25393620
- Ichimori K, King JD, Engels D, Yajima A, Mikhailov A, Lammie P, et al. Global programme to eliminate lymphatic filariasis: the processes underlying programme success. PLoS Negl Trop Dis. 2014 Dec;8(12):e3328. http://dx.doi.org/10.1371/journal.pntd.0003328 pmid: 25502758
- National master plan for neglected tropical diseases (NTDs). Addis Ababa: Ministry of Health; 2013. Available from: http://ntdenvision.org/sites/default/files/docs/national_ntd_master_plan_ethiopia_2013-2015_1.pdf [cited 2014 Apr 3].
- Deribe K, Cano J, Newport MJ, Golding N, Pullan RL, Sime H, et al. Mapping and modelling the geographical distribution and environmental limits of podoconiosis in Ethiopia. PLoS Negl Trop Dis. 2015 Jul;9(7):e0003946. http://dx.doi.org/10.1371/journal.pntd.0003946 pmid: 26222887
- Deribe K, Tomczyk S, Tekola-Ayele F. Ten years of podoconiosis research in Ethiopia. PLoS Negl Trop Dis. 2013;7(10):e2301. http://dx.doi.org/10.1371/journal.pntd.0002301 pmid: 24130908
- BIG Lottery funds fight against neglected tropical disease. Brighton: Brighton and Sussex Medical School; 2014. Available from: http://www.bsms.ac.uk/about/news/big-lottery-funds-fight-against-neglected-tropical-disease/ [cited 2015 May 3].
- Ayode D, McBride CM, de Heer HD, Watanabe E, Gebreyesus T, Tora A, et al. A qualitative study exploring barriers related to use of footwear in rural highland ethiopia: implications for neglected tropical disease control. PLoS Negl Trop Dis. 2013;7(4):e2199. http://dx.doi.org/10.1371/journal.pntd.0002199 pmid: 23638211
- Yakob B, Deribe K, Davey G. Health professionals’ attitudes and misconceptions regarding podoconiosis: potential impact on integration of care in southern Ethiopia. Trans R Soc Trop Med Hyg. 2010 Jan;104(1):42–7. http://dx.doi.org/10.1016/j.trstmh.2009.07.021 pmid: 19717176
- Varghese A, Glass C. Drug-shoe combination aims to stomp out Haiti’s neglected diseases [Internet]. Frontlines online edition. Washington: United States Agency for International Development; 2013. Available from: http://www.usaid.gov/news-information/frontlines/water-neglected-tropical-diseases/drug-shoe-combination-aims-stomp-out [cited 2014 Sep 11].