Opinion
VIEWPOINT
Peter J. Hotez, MD, PhD Sabin Vaccine Institute & Texas Children’s Hospital Center for Vaccine Development, Section of Pediatric Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas. Rosannah M. Velasquez, BS National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas. John E. Wolf Jr, MD Department of Dermatology, Baylor College of Medicine, Houston, Texas.
Corresponding Author: Peter J. Hotez, MD, PhD, National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 113, Houston, TX 77030 ([email protected]). jamadermatology.com
Neglected Tropical Skin Diseases Their Global Elimination Through Integrated Mass Drug Administration? In 2005, the concept of a combination of essential medicines—the “rapid-impact” package—was proposed to simultaneously target 7 high-prevalence neglected tropical diseases (NTDs) in sub-Saharan Africa through programs of annual mass drug administration.1 The approach relied on the observation that the major NTDs affecting the poorest people in sub-Saharan Africa, led by hookworm infection, ascariasis, schistosomiasis, trichuriasis, trachoma, lymphatic filariasis (LF), and onchocerciasis, have similarities in terms of their abilities to cause long-term disabilities and ultimately poverty by influencing worker productivity in the tropics and child development, as well as having effects on girls and women, especially during pregnancy. Moreover, these NTDs overlap geographically and therefore can be treated at roughly the same time through once-annual administration of an integrated package containing albendazole (or mebendazole), ivermectin, praziquantel, and azithromycin.1 Together, these medicines could be administered for less than US $1 annually, making this approach highly cost-effective. Today, under the framework of a 2013 World Health Assembly resolution, the World Health Organization estimates that more than 700 million people have received partial or complete rapid-impact packages annually.2 This milestone possibly represents one of the world’s largest health intervention programs. Critical to its success are generous donations of the NTD medicines from the major pharmaceutical companies, together with significant financial support from the governments of the United States and United Kingdom. Through integrated mass drug administration (also known as “preventive chemotherapy”), at least 3 of the 7 NTDs (namely, LF, onchocerciasis, and trachoma) are now prospects for possible elimination as global health problems, while the morbidity of the other NTDs targeted by the rapid-impact package also would be reduced. We are just beginning to understand how this scaled-up integrated mass drug administration approach could also have a major effect on reducing the global burden of human skin disease. Shown in the Table are 4 of the highest-prevalence NTDs that also exhibit significant cutaneous manifestations. They are ranked using a metric known as the disability-adjusted life year, a combination of the years of life lost and years lost through disability.3 While none of these NTDs are significant causes of mortality, they are important causes of disability in developing countries. The disabilityadjusted life years for almost 300 global health conditions were recently compiled through the Global Bur-
den of Disease Study 2010, which reveals that the disease burden of the 4 major NTDs with cutaneous manifestations is almost 5 million disability-adjusted life years, exceeding that of every other reported dermatologic condition (including psoriasis, cellulitis, acne vulgaris, alopecia areata, pruritus, urticaria, and decubitus ulcer), with the exception of eczema.3 Both LF and onchocerciasis, which have been specifically targeted for elimination by mass drug administration, have pronounced cutaneous manifestations. Lymphatic filariasis results in lymphedema of the legs, arms, and breasts with marked changes to overlying skin, while onchocercal skin disease is associated with intense pruritus and disfigurement. Some experts rank the skin manifestations as being at least as important as the blinding features of onchocerciasis, and both of these NTDs are linked with social stigma and discrimination, mostly due to their disfiguring features.4 Through mass drug administration with ivermectin or diethylcarbamazine, LF has been eliminated in more than 20 countries, while onchocerciasis has been eliminated in at least 2 African countries. In the Americas, transmission of onchocerciasis has been stopped except in 2 foci among indigenous populations along the Brazil-Venezuelan border. And the consequences of deploying rapid-impact packages now appear to be extending to other neglected tropical skin diseases. Two important examples are yaws and scabies. For yaws, single-dose oral azithromycin was revealed in 2012 to be as effective as the standard injection of benzathine penicillin.5 Accordingly, the World Health Organization convened a high-level meeting in 2012 to design a new yaws eradication strategy focusing on 6 of the most endemic countries: Cameroon, Ghana, Indonesia, Papua New Guinea, the Solomon Islands, and Vanuatu. The approach relies on village- or community-directed treatments with single-dose azithromycin, followed by 3 to 6 monthly retreatments.5 For scabies, infestation with the ectoparasitic mite Sarcoptes scabiei is associated with more than 1.5 million disability-adjusted life years (with the highest disease burden in the South Pacific and northern Australia) due to intense pruritus and secondary bacterial infections leading to pyoderma and post-streptococcal glomerulonephritis as long-term sequelae.6 Oral ivermectin was shown to have a cure rate exceeding 90% when given as 2 doses 8 to 15 days apart, leading to a proposed scabies elimination strategy based on 2 rounds of mass drug administration during a 2-week period.7 Mass drug administration with ivermectin in the Solomon Islands has reduced the scabies prevalence from 25% to 1%, and in JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
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481
Opinion Viewpoint
Table. Ranking of Neglected Tropical Diseases With Major Skin Manifestations Currently Targeted by Mass Drug Administration Ranking
Disease
DALYs Lost Annually
Major Geographic Areas or Affected Countries
Major Cutaneous Manifestations
1
Lymphatic filariasis
2 775 000
India, Indonesia, and Nigeria
Lymphedema and elephantiasis
Ivermectin + albendazole or diethylcarbamazine citrate + albendazole
2
Scabies
1 580 000
South Pacific and northern Australia
Pruritus, “7-year itch,” crusted scabies, and secondary pyoderma
Ivermectin and topical permethrin
3
Onchocerciasis
4
Yaws
Total DALYs
494 000 Not determined
Major MDA Approaches
Sub-Saharan Africa
Onchocercal skin disease
Ivermectin
Papua New Guinea, Solomon Islands, and Ghana
Cutaneous lesions with involvement of the bones and joints
Azithromycin
4 849 000
Abbreviations: DALYs, disability-adjusted life years; MDA, mass drug administration.
2012, an International Alliance for the Control of Scabies was established to advance the expansion of this and related approaches.7 Through expanded use of oral ivermectin, it may be possible to advance the control or elimination of several important dermatologic conditions, including onchocercal skin disease, the cutaneous manifestations of LF and scabies, and pyoderma. Mass drug administration of azithromycin is the key to yaws control or possibly eradication. For some areas of the world, especially sub-Saharan Africa, these medicines are being provided through administration of a rapid-impact package that targets several NTDs, including those that affect the skin.1,2 For other areas of the world, especially in Oceania, where scabies or yaws might be hyper-endemic, stand-alone
ARTICLE INFORMATION Published Online: March 26, 2014. doi:10.1001/jamadermatol.2013.8759. Conflict of Interest Disclosures: None reported. REFERENCES 1. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med. 2005;2(11):e336. 2. World Health Organization. Integrated preventive chemotherapy for neglected tropical
482
programs may be required using ivermectin or azithromycin, respectively. In the coming years, the global community of dermatologists will have an important role in ensuring the appropriate use of ivermectin and azithromycin to effectively reduce the burden of NTDrelated skin disease in developing countries. In addition, dermatologists will be needed to spearhead efforts to implement both correct diagnostic approaches and programs of monitoring and evaluation. Global initiatives for advocacy and mobilization of financial resources also may be required. In so doing, the dermatology community could have an unprecedented role in advancing the United Nations Millennium Development Goals.
diseases: estimation of the number of interventions required and delivered, 2009–2010. Wkly Epidemiol Rec. 2012;87(2):17-27.
5. World Health Organization. Eradication of yaws—the Morges strategy. Wkly Epidemiol Rec. 2012;87(20):189-194.
3. Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):21972223.
6. McLean FE. The elimination of scabies: a task for our generation. Int J Dermatol. 2013;52(10):12151223.
4. Zeldenryk LM, Gray M, Speare R, Gordon S, Melrose W. The emerging story of disability associated with lymphatic filariasis: a critical review. PLoS Negl Trop Dis. 2011;5(12):e1366.
7. Engelman D, Kiang K, Chosidow O, et al; Members of the International Alliance for the Control of Scabies. Toward the global control of human scabies: introducing the International Alliance for the Control of Scabies. PLoS Negl Trop Dis. 2013;7(8):e2167.
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
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jamadermatology.com
VIEWPOINT
Peter J. Hotez, MD, PhD Sabin Vaccine Institute & Texas Children’s Hospital Center for Vaccine Development, Section of Pediatric Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas. Rosannah M. Velasquez, BS National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas. John E. Wolf Jr, MD Department of Dermatology, Baylor College of Medicine, Houston, Texas.
Corresponding Author: Peter J. Hotez, MD, PhD, National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 113, Houston, TX 77030 ([email protected]). jamadermatology.com
Neglected Tropical Skin Diseases Their Global Elimination Through Integrated Mass Drug Administration? In 2005, the concept of a combination of essential medicines—the “rapid-impact” package—was proposed to simultaneously target 7 high-prevalence neglected tropical diseases (NTDs) in sub-Saharan Africa through programs of annual mass drug administration.1 The approach relied on the observation that the major NTDs affecting the poorest people in sub-Saharan Africa, led by hookworm infection, ascariasis, schistosomiasis, trichuriasis, trachoma, lymphatic filariasis (LF), and onchocerciasis, have similarities in terms of their abilities to cause long-term disabilities and ultimately poverty by influencing worker productivity in the tropics and child development, as well as having effects on girls and women, especially during pregnancy. Moreover, these NTDs overlap geographically and therefore can be treated at roughly the same time through once-annual administration of an integrated package containing albendazole (or mebendazole), ivermectin, praziquantel, and azithromycin.1 Together, these medicines could be administered for less than US $1 annually, making this approach highly cost-effective. Today, under the framework of a 2013 World Health Assembly resolution, the World Health Organization estimates that more than 700 million people have received partial or complete rapid-impact packages annually.2 This milestone possibly represents one of the world’s largest health intervention programs. Critical to its success are generous donations of the NTD medicines from the major pharmaceutical companies, together with significant financial support from the governments of the United States and United Kingdom. Through integrated mass drug administration (also known as “preventive chemotherapy”), at least 3 of the 7 NTDs (namely, LF, onchocerciasis, and trachoma) are now prospects for possible elimination as global health problems, while the morbidity of the other NTDs targeted by the rapid-impact package also would be reduced. We are just beginning to understand how this scaled-up integrated mass drug administration approach could also have a major effect on reducing the global burden of human skin disease. Shown in the Table are 4 of the highest-prevalence NTDs that also exhibit significant cutaneous manifestations. They are ranked using a metric known as the disability-adjusted life year, a combination of the years of life lost and years lost through disability.3 While none of these NTDs are significant causes of mortality, they are important causes of disability in developing countries. The disabilityadjusted life years for almost 300 global health conditions were recently compiled through the Global Bur-
den of Disease Study 2010, which reveals that the disease burden of the 4 major NTDs with cutaneous manifestations is almost 5 million disability-adjusted life years, exceeding that of every other reported dermatologic condition (including psoriasis, cellulitis, acne vulgaris, alopecia areata, pruritus, urticaria, and decubitus ulcer), with the exception of eczema.3 Both LF and onchocerciasis, which have been specifically targeted for elimination by mass drug administration, have pronounced cutaneous manifestations. Lymphatic filariasis results in lymphedema of the legs, arms, and breasts with marked changes to overlying skin, while onchocercal skin disease is associated with intense pruritus and disfigurement. Some experts rank the skin manifestations as being at least as important as the blinding features of onchocerciasis, and both of these NTDs are linked with social stigma and discrimination, mostly due to their disfiguring features.4 Through mass drug administration with ivermectin or diethylcarbamazine, LF has been eliminated in more than 20 countries, while onchocerciasis has been eliminated in at least 2 African countries. In the Americas, transmission of onchocerciasis has been stopped except in 2 foci among indigenous populations along the Brazil-Venezuelan border. And the consequences of deploying rapid-impact packages now appear to be extending to other neglected tropical skin diseases. Two important examples are yaws and scabies. For yaws, single-dose oral azithromycin was revealed in 2012 to be as effective as the standard injection of benzathine penicillin.5 Accordingly, the World Health Organization convened a high-level meeting in 2012 to design a new yaws eradication strategy focusing on 6 of the most endemic countries: Cameroon, Ghana, Indonesia, Papua New Guinea, the Solomon Islands, and Vanuatu. The approach relies on village- or community-directed treatments with single-dose azithromycin, followed by 3 to 6 monthly retreatments.5 For scabies, infestation with the ectoparasitic mite Sarcoptes scabiei is associated with more than 1.5 million disability-adjusted life years (with the highest disease burden in the South Pacific and northern Australia) due to intense pruritus and secondary bacterial infections leading to pyoderma and post-streptococcal glomerulonephritis as long-term sequelae.6 Oral ivermectin was shown to have a cure rate exceeding 90% when given as 2 doses 8 to 15 days apart, leading to a proposed scabies elimination strategy based on 2 rounds of mass drug administration during a 2-week period.7 Mass drug administration with ivermectin in the Solomon Islands has reduced the scabies prevalence from 25% to 1%, and in JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of North Dakota User on 05/15/2015
481
Opinion Viewpoint
Table. Ranking of Neglected Tropical Diseases With Major Skin Manifestations Currently Targeted by Mass Drug Administration Ranking
Disease
DALYs Lost Annually
Major Geographic Areas or Affected Countries
Major Cutaneous Manifestations
1
Lymphatic filariasis
2 775 000
India, Indonesia, and Nigeria
Lymphedema and elephantiasis
Ivermectin + albendazole or diethylcarbamazine citrate + albendazole
2
Scabies
1 580 000
South Pacific and northern Australia
Pruritus, “7-year itch,” crusted scabies, and secondary pyoderma
Ivermectin and topical permethrin
3
Onchocerciasis
4
Yaws
Total DALYs
494 000 Not determined
Major MDA Approaches
Sub-Saharan Africa
Onchocercal skin disease
Ivermectin
Papua New Guinea, Solomon Islands, and Ghana
Cutaneous lesions with involvement of the bones and joints
Azithromycin
4 849 000
Abbreviations: DALYs, disability-adjusted life years; MDA, mass drug administration.
2012, an International Alliance for the Control of Scabies was established to advance the expansion of this and related approaches.7 Through expanded use of oral ivermectin, it may be possible to advance the control or elimination of several important dermatologic conditions, including onchocercal skin disease, the cutaneous manifestations of LF and scabies, and pyoderma. Mass drug administration of azithromycin is the key to yaws control or possibly eradication. For some areas of the world, especially sub-Saharan Africa, these medicines are being provided through administration of a rapid-impact package that targets several NTDs, including those that affect the skin.1,2 For other areas of the world, especially in Oceania, where scabies or yaws might be hyper-endemic, stand-alone
ARTICLE INFORMATION Published Online: March 26, 2014. doi:10.1001/jamadermatol.2013.8759. Conflict of Interest Disclosures: None reported. REFERENCES 1. Molyneux DH, Hotez PJ, Fenwick A. “Rapid-impact interventions”: how a policy of integrated control for Africa’s neglected tropical diseases could benefit the poor. PLoS Med. 2005;2(11):e336. 2. World Health Organization. Integrated preventive chemotherapy for neglected tropical
482
programs may be required using ivermectin or azithromycin, respectively. In the coming years, the global community of dermatologists will have an important role in ensuring the appropriate use of ivermectin and azithromycin to effectively reduce the burden of NTDrelated skin disease in developing countries. In addition, dermatologists will be needed to spearhead efforts to implement both correct diagnostic approaches and programs of monitoring and evaluation. Global initiatives for advocacy and mobilization of financial resources also may be required. In so doing, the dermatology community could have an unprecedented role in advancing the United Nations Millennium Development Goals.
diseases: estimation of the number of interventions required and delivered, 2009–2010. Wkly Epidemiol Rec. 2012;87(2):17-27.
5. World Health Organization. Eradication of yaws—the Morges strategy. Wkly Epidemiol Rec. 2012;87(20):189-194.
3. Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):21972223.
6. McLean FE. The elimination of scabies: a task for our generation. Int J Dermatol. 2013;52(10):12151223.
4. Zeldenryk LM, Gray M, Speare R, Gordon S, Melrose W. The emerging story of disability associated with lymphatic filariasis: a critical review. PLoS Negl Trop Dis. 2011;5(12):e1366.
7. Engelman D, Kiang K, Chosidow O, et al; Members of the International Alliance for the Control of Scabies. Toward the global control of human scabies: introducing the International Alliance for the Control of Scabies. PLoS Negl Trop Dis. 2013;7(8):e2167.
JAMA Dermatology May 2014 Volume 150, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of North Dakota User on 05/15/2015
jamadermatology.com
