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Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengi adult worms in African cattle

de C Bronsvoort, Barend M.; Renz, Alfons; Tchakouté, Virginia; Tanya, Vincent N; Ekale, David and Trees, Alexander J (2005) Repeated high doses of avermectins cause prolonged sterilisation, but do not kill, Onchocerca ochengi adult worms in African cattle. Filaria Journal, 4 . Article Number: 8. ISSN 1475-2883

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Abstract

Background: Ivermectin (Mectizan™, Merck and CO. Inc.) is being widely used in the control of human onchocerciasis (Onchoverca volvulus) because of its potent effect on microfilariae. Human studies have suggested that, at the standard dose of 150 μg/kg an annual treatment schedule of ivermectin reversibly interferes with female worm fertility but is not macrofilaricidal. Because of the importance of determining whether ivermectin could be macrofilaricidal, the efficacy of high and prolonged doses of ivermectin and a related avermectin, doramectin, were investigated in cattle infected with O. ochengi. Methods: Drugs with potential macrofilaricidal activity, were screened for the treatment of human onchocerciasis, using natural infections of O. ochengi in African cattle. Three groups of 3 cows were either treated at monthly intervals (7 treatments) with ivermectin (Ivomec®, Merck and Co. Inc.) at 500 μg/kg or doramectin (Dectamax®, Pfizer) at 500 μg/ kg or not treated as controls. Intradermal nodules were removed at 6 monthly intervals and adult worms were examined for signs of drug activity. Results: There was no significant decline in nodule diameter, the motility of male and female worms, nor in male and female viability as determined by the ability to reduce tetrazolium, compared with controls, at any time up to 24 months from the start of treatments (mpt). Embryogenesis, however, was abrogated by treatment, which was seen as an accumulation of dead and dying intra-uterine microfilariae (mf) persisting for up to 18 mpt. Skin mf densities in treated animals had fallen to zero by <3 mpt, but by 18 mpt small numbers of mf were found in the skin of some treated animals and a few female worms were starting to produce multi-cellular embryonic stages. Follow-up of the doramectin treated group at 36 mpt showed that mf densities had still only regained a small proportion of their pre-treatment levels. Conclusion: These results have important implications for onchocerciasis control in the field. They suggest that ivermectin given at repeated high does may sterilise O. volvulus female worms for prolonged periods but is unlikely to kill them. This supports the view that control programmes may need to continue treatments with ivermectin for a period of decades and highlights the need to urgently identify new marcofiliaricidal compounds.

Item Type:Article
Additional Information:Published: 08 August 2005. 8 pages (page numbers not for citation purposes).
Uncontrolled Keywords:human onchocerciasis; Onchoverca volvulus; microfilariae; ivermectin; doramectin
Subjects:S Agriculture > SF Animal culture
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Veterinary Science > Department of Veterinary Clinical Science
Academic Faculties, Institutes and Research Centres > Liverpool School of Tropical Medicine
DOI:10.1186/1475-2883-4-8
Publisher's Statement:© 2005 deC Bronsvoort et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Related URLs:
Refereed:Yes
Status:Published
ID Code:775
Deposited On:09 Nov 2009 12:35
Last Modified:16 Apr 2013 17:10

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