Molyneux, David

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Perspective The NEW ENGLAND JOURNAL of MEDICINEmarch 29, 2012n engl j med 366;13 nejm.org march 29, 2012 1169Wuchereria bancrofti (and, in Asia, Brugia malayi and B. timori), which is transmitted by mosquitoes. The second principal cause is podo-coniosis.Lymphatic filariasis is endem-ic in some 72 countries through-out the tropics (see map), and an estimated 1.39 billion people live in areas of risk.1 An estimated 40 million people have stigmatiz-ing and disabling clinical manifes-tations of the infection: 15 mil-lion have elephantiasis, and some 25 million men have genital swell-ing, usually scrotal hydrocele.1 The current strategy for stopping transmission is the annual mass administration of donated drugs — albendazole and ivermectin in areas of Africa where onchocer-ciasis is coendemic, and diethyl-carbamazine and albendazole elsewhere.The Global Program to Elimi-nate Lymphatic Filariasis (GPELF), begun in 2000, is aimed at elimi-nating transmission of the infec-tion and reducing associated ill-nesses. Through annual mass distribution of drugs, substantial progress has been made in 12 years toward the elimination target set by the GPELF, with about 466 million people treated in 2010. The economic benefits accrued through the program from 2000 through 2008, in-cluding the ancillary benefits of  deworming and the impact on scabies, have been calculated at $24 billion. Costs per year for control of lymphatic filariasis range from $0.06 to $1.00 per person, depending on the set-ting; as with other neglected trop-ical diseases, costs of preventive chemotherapy are general ly less than $0.50 per person per year. Therefore, prevention of lymphatic filariasis ranks among the most cost-effective global health inter-ventions, along with deworming and onchocerciasis prevention, as measured in cost per disabil-ity-adjusted life-year averted.2Lymphatic filariasis is one of 17 neglected tropical diseases that afflict the world’s poorest peo-ple, but another even more ne-glected condition causing ele-phantiasis has been highlighted in recent years — podoconiosis, which affects some 4 million peo-ple in Africa, Latin America, and a few areas of Asia3 (see map). For many years, podoconiosis was relegated to the small print of even specialist tropical medicine Tropical Lymphedemas — Control and PreventionDavid H. Molyneux, Ph.D., D.Sc.Related article, p. 1200There are two principal causes of elephantiasis, or lymphedema, in the tropics. The most com-mon cause and a significant public health problem is lymphatic filariasis due to the parasitic nematode The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF LIVERPOOL on January 29, 2015. For personal use only. No other uses without permission.  Copyright © 2012 Massachusetts Medical Society. All rights reserved. PERSPECTIVEn engl j med 366;13 nejm.org march 29, 20121170textbooks, but it has emerged as an important cause of illness in communities where people are ex-posed to irritant, red-clay, volcanic soil. Microsilica particles from the soil enter the body through the skin of the feet and cause chronic obstruction of the lymphatics.The article by Tekola Ayele et al. in this issue of the Journal (pages 1200–1208) highlights the role of genetics in the predisposition to this condition. The authors found a significant association of podo-coniosis with particular genetic variants in the HLA class II re-gion, and they found that certain single-nucleotide polymorphisms increase the risk of clinical dis-ease by a factor of two to three. Affected people have symptoms similar to those associated with filarial lymphedema: adenolym-phangitis, plantar edema, moss-like papillomas (“mossy foot”), and multiple skin nodules, with progression to a hard, fibrotic leg (see photo). Podoconiosis must be distinguished from filarial lymphedema — it is found at alti-tudes higher than those at which mosquitoes can transmit filarial infection (a maximum of about 1500 m). The study by Tekola Ayele et al. highlights the importance of examining the human genetics of disease in resource-poor areas to enable the targeting of interven-tions, which in this case are as simple as providing shoes to peo-ple with a family history of podo-coniosis. Previous work in Ethi-opia revealed the social and economic effects of the disease — affected people have a markedly reduced earning capacity.More than 705 million people received integrated preventive che-motherapy for at least one ne-glected tropical disease in 2009, and 702 million to 715 million did so in 2010.4 More than 800 mil-lion people are treated annually for some form of helminth dis-ease or trachoma, according to the World Health Organization, and more than half of them are treated for lymphatic filariasis. Expansion of the lymphatic fila-riasis program in Central Africa, and in the Democratic Republic of the Congo and Cameroon in particular, is constrained by the risk of severe adverse reactions, manifested as encephalopathy, to treatment with ivermectin among persons with high microfilarial loads of the tropical eye worm Loa loa. This problem was initially identified in onchocerciasis-con-trol programs during the mid-1990s and has prevented large-Tropical Lymphedemas — Control and PreventionLF-endemic countries and territories implementing MDALF-endemic countries and territories where the target was achieved and MDA stoppedOther LF-endemic countries and territoriesNon–LF-endemic countries and territoriesNo information availableCountries where podoconiosis is endemic or has been described Global Distribution of Lymphatic Filariasis (LF) and Podoconiosis and Status of Mass Administration of Drugs (MDA), 2009.Data are from the World Health Organization. Dots represent various island nations.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF LIVERPOOL on January 29, 2015. For personal use only. No other uses without permission.  Copyright © 2012 Massachusetts Medical Society. All rights reserved. n engl j med 366;13 nejm.org march 29, 2012PERSPECTIVE1171scale treatment for lymphatic filariasis because of the potential coendemicity of W. bancrofti and L. loa in Central Africa.Whereas annual mass drug ad-ministration relies on the ability of drugs to reduce microfilaria loads to levels at which transmis-sion is reduced, a high-priority need is for a drug that kills or permanently sterilizes the adult worms — a macrofilaricide. It is known that some filarial nema-todes contain the endosymbiotic bacteria wolbachia, which have become targets for chemother-apy, since they have also been implicated as contributors to the pathogenesis of inflammatory disease. Doxycycline is effective when given daily over a 6-week period, since it kills or sterilizes adult filaria of both Onchocerca volvulus and W. bancrofti. Ongoing research is seeking to reduce the duration of antibiotic treatment and to find a less toxic product that might be given over a short-er period and be amenable to ad-ministration by the communities themselves, as treatments for on-chocerciasis and lymphatic filari-asis are. Although the current drugs (albendazole, ivermectin, and diethylcarbamazine) are de-signed to be given for the dura-tion of the adult worms’ life (an estimated 5 to 8 years) and at a coverage level of 75% of the pop-ulation in all geographic areas where they are endemic, they also have an effect on clinical disease: they reduce the frequency of fi-larial fevers, the size of scrotal hydrocele, and in children, sub-clinical lymphatic damage.One of the challenges for the GPELF has been that disease-control programs that address the needs of patients with exist-ing clinical lymphedema or hydro-cele have lagged behind mass drug distribution. It is critical that this gap be addressed. The drivers of success will be maintenance of high coverage, provision of re-sources for monitoring and eval-uation, and efforts to understand the complexity of the interactions among coendemic conditions such as lymphatic filariasis, onchocer-ciasis, and soil-transmitted hel-minths; control or elimination interventions for all these condi-tions benefit from donated drugs. The success of lymphatic filaria-sis programs in Africa will also be influenced by the extent of coverage with bed nets impreg-nated with long-lasting insecti-cide, which, if distributed widely, could probably reduce the required number of annual mass drug ad-ministrations.Over the past decade, there has been remarkable progress in addressing lymphatic filariasis as a global problem. Several billion doses of drugs have been donated and delivered, and they have had the additional benefit of effective deworming. Still, programs pro-viding surgery for scrotal hydro-cele need to be scaled up, and access to lymphedema-manage-ment programs must be increased. The lymphatic filariasis commu-nity is aware of the need for  improved therapy, especially a macrofilaricide, as well as the challenges of scaling up programs in countries that are recovering from conflict and civil unrest and of the need to expand dis-ease control, address the L. loa issue, enhance coverage, and monitor and evaluate impact. Certification of the absence of transmission awaits detailed transmission-assessment surveys. Research into improving the cost-effectiveness of elimination pro-grams will continue, and their lessons need to be not only learned but also applied.The two tropical lymphedemas, filariasis and podoconiosis, are now on the radar screen for global health. The two conditions share clinical features and challenges that are similar to highly dis-abling conditions affecting the most disadvantaged communities, and they inflict similar social problems. It may be possible, however, to eliminate both dis-eases. The idea that impover-ished people might wear shoes may seem self-evident, but being able to target the people at great-est risk represents considerable progress.Disclosure forms provided by the author are available with the full text of this arti-cle at NEJM.org.From the Centre for Neglected Tropical Dis-eases, Liverpool School of Tropical Medi-cine, Liverpool, United Kingdom.1. Global programme to eliminate lymphatic filariasis: progress report on mass drug ad-ministration, 2010. Wkly Epidemiol Rec 2011;86:377-88.2. Ottesen EA, Hooper PJ, Bradley M, Biswas G. The global programme to eliminate lym-phatic filariasis: health impact after 8 years. PLoS Negl Trop Dis 2008;2(10):e317.3. Davey G, Newport M. Podoconiosis: the most neglected tropical disease? Lancet 2007;369:888-9.4. Integrated preventive chemotherapy for neglected tropical diseases: estimation of the number of interventions required and delivered, 2009–2010. Wkly Epidemiol Rec 2012;87:17-27.Copyright © 2012 Massachusetts Medical Society.Tropical Lymphedemas — Control and PreventionLegs of a Man with Lymphatic Filariasis.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY OF LIVERPOOL on January 29, 2015. For personal use only. No other uses without permission.  Copyright © 2012 Massachusetts Medical Society. All rights reserved. 

Tropical Lymphedemas — Control and Prevention

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Tropical Lymphedemas — Control and Prevention

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