IVM Alone vs ALB + IVM Against Onchocerciasis

Summary

Onchocerciasis is a vector-borne nematode parasitic disease that causes severe disability. Onchocerciasis affects approximately 33 million people, mostly in 30 countries in sub-Saharan Africa (with small foci in Latin America and Yemen) 1This disease causes blindness and severe skin disease and it is spread by black flies. O. volvulus adult worms live in subcutaneous nodules. O. volvulus adult worms are larger and less sensitive to available drug treatments than those of the species that cause Lymphatic Filariasis (LF). They also have a longer lifespan (approximately 14 years rather than the estimated 7 years for LF parasites). Several programs and developments have greatly improved the Onchocerciasis. situation since the 1970's when the Onchocerciasis Control Programme (OCP) in West Africa (green countries in the map) was initiated. OCP relied exclusively on vector (black fly) control in its early years. However, following the appearance of Ivermectin (Mectizan) on the scene in the late 1980's, OCP transitioned to become a drug distribution program with annual IVM MDA in 11 countries. OCP ended in 2002. This was replaced by the African Program for Onchocerciasis Control (APOC) which coordinates community directed distribution of IVM MDA in 28 African countries (including the former OCP countries). OCP and APOC have done a good job of reducing parasite infection intensities and Onchocerciasis disease rates in many endemic countries. Unfortunately, there is no real end in sight for the APOC approach (apart from a funding endpoint in 2015); while it may be possible to eliminate Onchocerciasis. In selected areas by MDA with IVM (alone, or combined with vector control), disease control programs in most African countries will require active maintenance for many years to come. While IVR has good activity against the parasite larvae that cause disease in the skin and eye (microfilariae or Mf), it does not kill O. volvulus adult worms, and they resume production of Mf that can lead to transmission of new Onchocerciasis. Cases by black flies after a few months. APOC activities are focused on areas with high infection rates (where disease risks are highest). However, extensive areas in Africa where fewer than 20% of adult men have Onchocerciasis nodules detectable by palpation are not receiving interventions for Onchocerciasis at this time. These areas are not disease free. (Onchocerciasis dermatitis can be severe in hypoendemic areas), and they also may serve as a source for reintroduction of the parasite into previously controlled areas after interventions stop.

Timeline

Start

2012-04

Primary completion

2015-04

Completion

2016-10

Publications

• Background Basanez MG, Pion SD, Churcher TS, Breitling LP, Little MP, Boussinesq M. River blindness: a success story under threat? PLoS Med. 2006 Sep;3(9):e371. doi: 10.1371/journal.pmed.0030371.
• Background Gardon J, Boussinesq M, Kamgno J, Gardon-Wendel N, Demanga-Ngangue, Duke BO. Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet. 2002 Jul 20;360(9328):203-10. doi: 10.1016/S0140-6736(02)09456-4.
• Background Zahner H, Schares G. Experimental chemotherapy of filariasis: comparative evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and B. pahangi. Acta Trop. 1993 Jan;52(4):221-66. doi: 10.1016/0001-706x(93)90010-9.
• Background Awadzi K, Hero M, Opoku O, Buttner DW, Gilles HM. The chemotherapy of onchocerciasis. XV. Studies with albendazole. Trop Med Parasitol. 1991 Dec;42(4):356-60.
• Background Awadzi K, Addy ET, Opoku NO, Plenge-Bonig A, Buttner DW. The chemotherapy of onchocerciasis XX: ivermectin in combination with albendazole. Trop Med Parasitol. 1995 Dec;46(4):213-20.
• Background Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT. The co-administration of ivermectin and albendazole--safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2003 Mar;97(2):165-78. doi: 10.1179/000349803235001697.
• Background Horton J, Witt C, Ottesen EA, Lazdins JK, Addiss DG, Awadzi K, Beach MJ, Belizario VY, Dunyo SK, Espinel M, Gyapong JO, Hossain M, Ismail MM, Jayakody RL, Lammie PJ, Makunde W, Richard-Lenoble D, Selve B, Shenoy RK, Simonsen PE, Wamae CN, Weerasooriya MV. An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis. Parasitology. 2000;121 Suppl:S147-60. doi: 10.1017/s0031182000007423.
• Background Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. doi: 10.1097/00001432-200212000-00008.
• Background Geary TG. Ivermectin 20 years on: maturation of a wonder drug. Trends Parasitol. 2005 Nov;21(11):530-2. doi: 10.1016/j.pt.2005.08.014. Epub 2005 Aug 26.
• Background Moreno Y, Nabhan JF, Solomon J, Mackenzie CD, Geary TG. Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20120-5. doi: 10.1073/pnas.1011983107. Epub 2010 Nov 1.
• Background Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.
• Background Kitzman D, Wei SY, Fleckenstein L. Liquid chromatographic assay of ivermectin in human plasma for application to clinical pharmacokinetic studies. J Pharm Biomed Anal. 2006 Mar 3;40(4):1013-20. doi: 10.1016/j.jpba.2005.08.026. Epub 2005 Oct 19.
• Background Cringoli G, Rinaldi L, Maurelli MP, Utzinger J. FLOTAC: new multivalent techniques for qualitative and quantitative copromicroscopic diagnosis of parasites in animals and humans. Nat Protoc. 2010 Mar;5(3):503-15. doi: 10.1038/nprot.2009.235. Epub 2010 Feb 25.

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