Onchocerciasis: the beginning of the end

Onchocerciasis: the beginning of the end Elimination, Lymphatic filariasis, Mectizan Donation Program, Non-governmental organizations, Onchocerciasis Thirty years ago, the concept that onchocerciasis could be eliminated worldwide was unthinkable. Today, we’re on the road to seeing the end of this debilitating disease. Thanks to the efforts of a global partnership consisting of MSD, also known as Merck & Co., Inc., Kenilworth, NJ USA, the Mectizan Donation Program (MDP), endemic countries, bilateral funding agencies and the donor community, the World Health Organization (WHO), non-governmental organizations (NGOs) and researchers, the disease is on the decline. In areas that have been under treatment the longest, the blindness, visual impairment, skin disease and itching caused by onchocerciasis is now increasingly rare. Onchocerciasis is transmitted by repeated bites of Simulium blackflies that breed near fast-flowing rivers, hence the common name ‘river blindness’. The disease, caused by the filarial nematode Onchocerca volvulus, is currently found in the Americas in Brazil and Venezuela, in 28 countries in sub-Saharan Africa and in Yemen. Currently the WHO estimates that 198 million people are at risk of infection and an estimated 17 million people are thought to be infected.1 In the late 1970s, MSD scientists studied a collection of microorganisms. One of them produced a powerful anti-parasitic compound, which was modified and developed as ivermectin. The microorganisms had been received from the Kitasato Institute, where they had been isolated from soil. Ivermectin's anti-parasitic success in animals led MSD's Dr William Campbell to suggest its use in humans for O. volvulus. Prior to this development, the drug treatments available for the treatment of onchocerciasis caused severe side effects and could not be used in mass administration. Clinical trials demonstrated ivermectin’s efficacy for the disease and it was registered with the French regulatory agency under the name Mectizan. For this achievement, Dr. Campbell and Dr. Satoshi Omura of the Kitasato Institute shared the 2015 Nobel Prize in Physiology or Medicine. In 1987, MSD announced that it would donate the drug free of charge to ‘all who need it for as long as needed’. As we are shifting from control to the elimination of transmission of onchocerciasis where feasible, this special supplement addresses a range of issues relating to onchocerciasis elimination, including diagnostics, mapping, laboratory support, alternative treatment strategies, the role of NGOs and national onchocerciasis elimination committees and evidence of elimination in the Americas and in African settings (Uganda). The purpose of this publication is to provide proof of concept that, through a strong partnership between MSD’s donation of Mectizan, the endemic countries and donors, we can eliminate onchocerciasis, a scourge that was once classified as a disease that could only be controlled. In the Americas, the goal was always elimination. The small, relatively isolated foci and inefficient vector in the region made elimination feasible and was first demonstrated by Colombia in 2013, followed by Ecuador in 2014, Mexico in 2015 and Guatemala in 2016. Elimination success has been achieved in Africa as well. Countries including Ethiopia, Mali, Niger, Senegal, Sudan and Uganda have eliminated transmission of onchocerciasis in subnational areas. In some of these countries, alternative treatment strategies have been adopted, demonstrating that targeted strategies tailored to specific regions can accelerate progress toward elimination. One of the most important recent developments at the country level is the formation of national onchocerciasis elimination committees (NOECs) whose role is described in the supplement by Griswold et al.2 Country ownership of the elimination effort is critical to sustaining the progress made thus far and to achieving adequate geographic and therapeutic coverage necessary to eliminate the disease. Uganda was the first to establish an NOEC in 2008, which proved an excellent model; Ethiopia established its committee in 2014. Ministries of health and other partners agree that NOECs facilitate the development of national elimination guidelines and the provision of technical assistance for scale-up of mass drug administration, impact surveys and the implementation of twice-yearly treatment with Mectizan where appropriate. MSD’s sustained commitment to the donation of Mectizan for onchocerciasis is remarkable considering the massive scale-up of treatments shipped annually. Today, the MDP is the longest-running drug donation program of its kind. In 2016, 167.9 million treatments were approved for onchocerciasis elimination in 23 countries in Africa and in Brazil, Venezuela and Yemen. The supplement includes a look back at the past 30 years of Mectizan donation provided by Gustavsen et al.3 We also examine the next steps for stopping treatment in the progress toward elimination. Technical assistance to endemic countries provided by the WHO is another key element in the shift from control to elimination. The supplement includes a look at planning for the future of elimination in Africa by the WHO and WHO Regional Office for Africa colleagues. Quality laboratory support in Africa is also essential for assessing the transmission status of onchocerciasis, which is presented by Shott et al.4 Several challenges must be overcome before onchocerciasis elimination can be achieved. Civil unrest, hard-to-reach rural populations, co-endemicity with loiasis and cross-border transmission are examples of challenges that require partnership and collaboration. Multiple partners have worked to find innovative solutions to the treatment of onchocerciasis in Loa loa-endemic areas where Mectizan cannot be safely used, as adverse events have been reported in heavily co-infected patients. The loiasis problem is presented in this supplement by Kamgno et al.5 and cross-border transmission of onchocerciasis between countries requiring intercountry collaboration is addressed by Bush et al.6 Finally, we learn about the contributions of our NGO partners, without whom the massive scale-up of mass drug distribution would not have been possible. As Hopkins7 points out in an article published in International Health in 2016, NGO partners have been essential to implementing the community-directed treatment with ivermectin (CDTI) strategy that has been a major catalyst for the massive scale-up of treatment. CDTI was developed by the WHO’s Special Program for Research and Training in Tropical Diseases and African Program for Onchocerciasis Control and is now being adopted by other disease programs. NGOs also play a key role in advocacy and resource mobilization for onchocerciasis elimination. This is the beginning of the end of onchocerciasis. After 30 years of Mectizan and onchocerciasis control, countries are now advocating for a new World Health Assembly resolution calling for the elimination of onchocerciasis worldwide to replace resolution WHA 47.32, which called for onchocerciasis control. This is an exciting development resulting from the unanticipated impact of Mectizan on the disease. Now that disease manifestations are increasingly rare, we must ensure that countries and communities remain committed and that the message is clear: continued success through high treatment and geographic coverage means a future free of the suffering caused by onchocerciasis. Authors’ contributions: JL developed the structure of the manuscript and developed the first draft, which was reviewed and revised by YS. All authors read and approved the final manuscript. JL is guarantor for the paper. References 1 Cantey P, editor. Progress report on the elimination of human onchocerciasis, 2016–2017. Geneva: World Health Organization, 2017. 2 Griswold E, Unnasch T, Eberhard M et al.  . The role of national committees in eliminating onchocerciasis. Int Health  2018; 10: i60– 70. Google Scholar CrossRef Search ADS PubMed  3 Gustavsen KM, Colatrella BD, McCoy T. For as long as necessary examining 30 years of MSD’s focus on achieving elimination of onchocerciasis and lymphatic filariasis. Int Health  2018; 10: i3– 6. Google Scholar CrossRef Search ADS PubMed  4 Shott J, Ducker C, Unnosch TR, Mackenzie CD. Establishing quality laboratory support for onchocerciasis elimination in Africa. Int Health 2018. 5 Kamgno J, Nana-Djeunga HC, Pion SD et al.  . Operationalization of the test and not treat strategy to accelerate the elimination of onchocerciasis and lymphatic filariasis in Central Africa. Int Health  2018; 10: i49– 53. Google Scholar CrossRef Search ADS PubMed  6 Bush S, Sodahlon Y, Downs P et al.  . Cross-border issues: an important component of onchocerciasis elimination programmes. Int Health  2018; 10: i54– 9. Google Scholar CrossRef Search ADS PubMed  7 Hopkins AD. Neglected tropical diseases in Africa: a new paradigm. Int Health  2016; 8: i28– 33. Google Scholar CrossRef Search ADS PubMed  © The Author 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Health Oxford University Press

Onchocerciasis: the beginning of the end

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© The Author 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Abstract

Elimination, Lymphatic filariasis, Mectizan Donation Program, Non-governmental organizations, Onchocerciasis Thirty years ago, the concept that onchocerciasis could be eliminated worldwide was unthinkable. Today, we’re on the road to seeing the end of this debilitating disease. Thanks to the efforts of a global partnership consisting of MSD, also known as Merck & Co., Inc., Kenilworth, NJ USA, the Mectizan Donation Program (MDP), endemic countries, bilateral funding agencies and the donor community, the World Health Organization (WHO), non-governmental organizations (NGOs) and researchers, the disease is on the decline. In areas that have been under treatment the longest, the blindness, visual impairment, skin disease and itching caused by onchocerciasis is now increasingly rare. Onchocerciasis is transmitted by repeated bites of Simulium blackflies that breed near fast-flowing rivers, hence the common name ‘river blindness’. The disease, caused by the filarial nematode Onchocerca volvulus, is currently found in the Americas in Brazil and Venezuela, in 28 countries in sub-Saharan Africa and in Yemen. Currently the WHO estimates that 198 million people are at risk of infection and an estimated 17 million people are thought to be infected.1 In the late 1970s, MSD scientists studied a collection of microorganisms. One of them produced a powerful anti-parasitic compound, which was modified and developed as ivermectin. The microorganisms had been received from the Kitasato Institute, where they had been isolated from soil. Ivermectin's anti-parasitic success in animals led MSD's Dr William Campbell to suggest its use in humans for O. volvulus. Prior to this development, the drug treatments available for the treatment of onchocerciasis caused severe side effects and could not be used in mass administration. Clinical trials demonstrated ivermectin’s efficacy for the disease and it was registered with the French regulatory agency under the name Mectizan. For this achievement, Dr. Campbell and Dr. Satoshi Omura of the Kitasato Institute shared the 2015 Nobel Prize in Physiology or Medicine. In 1987, MSD announced that it would donate the drug free of charge to ‘all who need it for as long as needed’. As we are shifting from control to the elimination of transmission of onchocerciasis where feasible, this special supplement addresses a range of issues relating to onchocerciasis elimination, including diagnostics, mapping, laboratory support, alternative treatment strategies, the role of NGOs and national onchocerciasis elimination committees and evidence of elimination in the Americas and in African settings (Uganda). The purpose of this publication is to provide proof of concept that, through a strong partnership between MSD’s donation of Mectizan, the endemic countries and donors, we can eliminate onchocerciasis, a scourge that was once classified as a disease that could only be controlled. In the Americas, the goal was always elimination. The small, relatively isolated foci and inefficient vector in the region made elimination feasible and was first demonstrated by Colombia in 2013, followed by Ecuador in 2014, Mexico in 2015 and Guatemala in 2016. Elimination success has been achieved in Africa as well. Countries including Ethiopia, Mali, Niger, Senegal, Sudan and Uganda have eliminated transmission of onchocerciasis in subnational areas. In some of these countries, alternative treatment strategies have been adopted, demonstrating that targeted strategies tailored to specific regions can accelerate progress toward elimination. One of the most important recent developments at the country level is the formation of national onchocerciasis elimination committees (NOECs) whose role is described in the supplement by Griswold et al.2 Country ownership of the elimination effort is critical to sustaining the progress made thus far and to achieving adequate geographic and therapeutic coverage necessary to eliminate the disease. Uganda was the first to establish an NOEC in 2008, which proved an excellent model; Ethiopia established its committee in 2014. Ministries of health and other partners agree that NOECs facilitate the development of national elimination guidelines and the provision of technical assistance for scale-up of mass drug administration, impact surveys and the implementation of twice-yearly treatment with Mectizan where appropriate. MSD’s sustained commitment to the donation of Mectizan for onchocerciasis is remarkable considering the massive scale-up of treatments shipped annually. Today, the MDP is the longest-running drug donation program of its kind. In 2016, 167.9 million treatments were approved for onchocerciasis elimination in 23 countries in Africa and in Brazil, Venezuela and Yemen. The supplement includes a look back at the past 30 years of Mectizan donation provided by Gustavsen et al.3 We also examine the next steps for stopping treatment in the progress toward elimination. Technical assistance to endemic countries provided by the WHO is another key element in the shift from control to elimination. The supplement includes a look at planning for the future of elimination in Africa by the WHO and WHO Regional Office for Africa colleagues. Quality laboratory support in Africa is also essential for assessing the transmission status of onchocerciasis, which is presented by Shott et al.4 Several challenges must be overcome before onchocerciasis elimination can be achieved. Civil unrest, hard-to-reach rural populations, co-endemicity with loiasis and cross-border transmission are examples of challenges that require partnership and collaboration. Multiple partners have worked to find innovative solutions to the treatment of onchocerciasis in Loa loa-endemic areas where Mectizan cannot be safely used, as adverse events have been reported in heavily co-infected patients. The loiasis problem is presented in this supplement by Kamgno et al.5 and cross-border transmission of onchocerciasis between countries requiring intercountry collaboration is addressed by Bush et al.6 Finally, we learn about the contributions of our NGO partners, without whom the massive scale-up of mass drug distribution would not have been possible. As Hopkins7 points out in an article published in International Health in 2016, NGO partners have been essential to implementing the community-directed treatment with ivermectin (CDTI) strategy that has been a major catalyst for the massive scale-up of treatment. CDTI was developed by the WHO’s Special Program for Research and Training in Tropical Diseases and African Program for Onchocerciasis Control and is now being adopted by other disease programs. NGOs also play a key role in advocacy and resource mobilization for onchocerciasis elimination. This is the beginning of the end of onchocerciasis. After 30 years of Mectizan and onchocerciasis control, countries are now advocating for a new World Health Assembly resolution calling for the elimination of onchocerciasis worldwide to replace resolution WHA 47.32, which called for onchocerciasis control. This is an exciting development resulting from the unanticipated impact of Mectizan on the disease. Now that disease manifestations are increasingly rare, we must ensure that countries and communities remain committed and that the message is clear: continued success through high treatment and geographic coverage means a future free of the suffering caused by onchocerciasis. Authors’ contributions: JL developed the structure of the manuscript and developed the first draft, which was reviewed and revised by YS. All authors read and approved the final manuscript. JL is guarantor for the paper. References 1 Cantey P, editor. Progress report on the elimination of human onchocerciasis, 2016–2017. Geneva: World Health Organization, 2017. 2 Griswold E, Unnasch T, Eberhard M et al.  . The role of national committees in eliminating onchocerciasis. Int Health  2018; 10: i60– 70. Google Scholar CrossRef Search ADS PubMed  3 Gustavsen KM, Colatrella BD, McCoy T. For as long as necessary examining 30 years of MSD’s focus on achieving elimination of onchocerciasis and lymphatic filariasis. Int Health  2018; 10: i3– 6. Google Scholar CrossRef Search ADS PubMed  4 Shott J, Ducker C, Unnosch TR, Mackenzie CD. Establishing quality laboratory support for onchocerciasis elimination in Africa. Int Health 2018. 5 Kamgno J, Nana-Djeunga HC, Pion SD et al.  . Operationalization of the test and not treat strategy to accelerate the elimination of onchocerciasis and lymphatic filariasis in Central Africa. Int Health  2018; 10: i49– 53. Google Scholar CrossRef Search ADS PubMed  6 Bush S, Sodahlon Y, Downs P et al.  . Cross-border issues: an important component of onchocerciasis elimination programmes. Int Health  2018; 10: i54– 9. Google Scholar CrossRef Search ADS PubMed  7 Hopkins AD. Neglected tropical diseases in Africa: a new paradigm. Int Health  2016; 8: i28– 33. Google Scholar CrossRef Search ADS PubMed  © The Author 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Journal

International HealthOxford University Press

Published: Mar 1, 2018

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