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Bronsvoort, B. M. D., Makepeace, Benjamin L., Renz, A., Tanya, V. N., Fleckenstein, L., Ekale, D. and Trees, Alexander J. (2008) 'UMF-078: A modified flubendazole with potent macrofilaricidal activity against Onchocerca ochengi in African cattle'. Parasites & Vectors, Vol 1, e18.
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Abstract
Background
Human onchocerciasis or river blindness, caused by the filarial nematode Onchocerca volvulus, is currently controlled using the microfilaricidal drug, ivermectin. However, ivermectin does not kill adult O. volvulus, and in areas with less than 65% ivermectin coverage of the population, there is no effect on transmission. Therefore, there is still a need for a macrofilaricidal drug. Using the bovine filarial nematode O. ochengi (found naturally in African cattle), the macrofilaricidal efficacy of the modified flubendazole, UMF-078, was investigated.
Methods: Groups of 3 cows were treated with one of the following regimens: (a) a single dose of UMF-078 at 150 mg/kg intramuscularly (im), (b) 50 mg/kg im, (c) 150 mg/kg intraabomasally (ia), (d) 50 mg/kg ia, or (e) not treated (controls).
Results
After treatment at 150 mg/kg im, nodule diameter, worm motility and worm viability (as measured by metabolic reduction of tetrazolium to formazan) declined significantly compared with pre-treatment values and concurrent controls. There was abrogation of embryogenesis and death of all adult worms by 24 weeks post-treatment (pt). Animals treated at 50 mg/kg im showed a decline in nodule diameter together with abrogated reproduction, reduced motility, and lower metabolic activity in isolated worms, culminating in approximately 50% worm mortality by 52 weeks pt. Worms removed from animals treated ia were not killed, but exhibited a temporary embryotoxic effect which had waned by 12 weeks pt in the 50 mg/kg ia group and by 24 weeks pt in the 150 mg/kg ia group. These differences could be explained by the different absorption rates and elimination half-lives for each dose and route of administration.
Conclusion
Although we did not observe any signs of mammalian toxicity in this trial with a single dose, other studies have raised concerns regarding neuro- and genotoxicity. Consequently, further evaluation of this compound has been suspended. Nonetheless, these results validate the molecular target of the benzimidazoles as a promising lead for rational design of macrofilaricidal drugs.
| Item Type: | Article |
|---|---|
| Additional Information: | The electronic version of this article is the complete one and can be found online at: http://www.parasitesandvectors.com/content/1/1/18 |
| Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 253 Anthelmintics W General Medicine. Health Professions > W 20.55.V4 Veterinary biomedical research WW Ophthalmology > Diseases. Color Perception > WW 160 Eye infections. Hypersensitivity diseases (General or not elsewhere classified) |
| Faculty: Department: | Groups (2002 - 2012) > Veterinary Parasitology Group (2002-2008) |
| Digital Object Identifer (DOI): | https://doi.org/10.1186/1756-3305-1-18 |
| Depositing User: | Ms Julia Martin |
| Date Deposited: | 27 Jul 2010 15:56 |
| Last Modified: | 17 Jul 2020 10:57 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/741 |
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